National Cancer Institute®
Last Modified: November 21, 2001
UI - 21356552
AU - Mineo TC; Ambrogi V; Corsaro V; Roselli M
TI - Postoperative adjuvant therapy for stage IB non-small-cell lung cancer.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):378-84
AD - Department of Thoracic Surgery, Tor Vergata University, Rome, Italy. email@example.com
OBJECTIVE: Although surgical resection alone is considered adequate treatment in stage IB non-small-cell lung cancer (NSCLC), long-term survival is not satisfactory and the recurrence rate is quite high. The validity of postoperative chemotherapy at stage IB in terms of disease-free and overall survival was assessed in a randomised trial. METHODS: The trial was designed as a randomised, two-group study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure. Chemotherapy consisted of treatment with cisplatin (100 mg/m(2) on day 1) and etoposide (120 mg/m(2) on days belonged to the adjuvant chemotherapy group and 33 to the control group. Groups were homogeneous for conventional risk factors. There was no clinical significant morbidity associated to chemotherapy. Patients were followed for a minimum period of 5 years. The rates of locoregional recurrence and distant metastases were 18 and 30%, respectively, in the adjuvant chemotherapy group and 24 and 43%, respectively, in the control group. The 5-year disease-free survival rates were 59% in the adjuvant group and 30% in the control group (P = 0.02). The difference in the Kaplan--Meier survival between the groups was significant as assessed using the log-rank test (P = 0.04). CONCLUSIONS: Our results suggest that adjuvant chemotherapy may reduce recurrences and prolong overall survival in patients at stage IB NSCLC deemed radically operated. Despite being difficult to accept, the use of adjuvant chemotherapy might have better long-term results.
UI - 21356554
AU - Lewinski T; Zulawski M; Turski C; Pietraszek A
TI - Small cell lung cancer I--III A: cytoreductive chemotherapy followed by resection with continuation of chemotherapy.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):391-8
AD - Department of Lung and Thoracic Tumors, The Maria Sklodowska--Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
OBJECTIVES: To define the place for surgery in combined modality treatment of small cell lung cancer patients. The endpoint was: does complete resection reduce the risk of local failure? METHODS: Between with a bulky cN2 tumor at presentation, were exposed to VP-16 based cytoreductive chemotherapy. After three courses of induction treatment, 46 patients underwent thoracotomy and 35 of them had resection. RESULTS: There were two sudden deaths (pulmonary embolism). No other complications were observed. In six cases (6/35 = 16%), no residual tumor was found in the resected specimen. Four weeks after surgery, chemotherapy was resumed. Three patients experienced local relapse (3/33), among them, the single patient with incomplete resection, and two other patients developed local and distant failure (2/33). Thus, the local relapse rate was 15% (5/33). Eight patients, mainly with chemotherapy induced surgicopathological complete remission (pCR) and with lymph nodes free of tumor in surgical specimens (pN0), are alive, tumor-free, at a median of 136 + months. Two patients died tumor-free at 65 and 147 months. One patient died of unrelated causes at 21 months with no evidence of disease at autopsy. The median survival in the cN0 + N1 subsets was 25.09 months, whereas in cN2 disease, this was 13.75 months. There were no long-term survivors among the patients with persistent N2 disease. The median survival in all 35 patients using the Kaplan--Meier method was 18 months; the 5-year tumor-free survival rate was 29% and the 10-year tumor-free survival rate was 23%. CONCLUSIONS: Satisfactory local tumor control confirmed the assumption of the study. No residual tumor in the resected specimen (pCR) is the most favorable prognostic factor and determinant of long-term survival. Surgery should not be performed in the patients with persistent N2 disease.
UI - 21436101
AU - Graziano SL; Tatum A; Herndon JE 2nd; Box J; Memoli V; Green MR; Kern JA
TI - Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):115-23
AD - Division of Hematology-Oncology, Department of Medicine, Regional Oncology Center, SUNY-Upstate Medical University and Veterans Affairs Medical Center, Syracuse, NY 13210, USA.
Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.
UI - 21436111
AU - Thomas CR Jr; Giroux DJ; Janaki LM; Turrisi AT 3rd; Crowley JJ; Taylor
TI - SA; McCracken JD; Shankir Giri PG; Gordon W Jr; Livingston RB; Gandara DR Ten-year follow-up of Southwest Oncology Group 8269: a phase II trial of concomitant cisplatin-etoposide and daily thoracic radiotherapy in limited small-cell lung cancer.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):213-9
AD - Department of Radiation Oncology, San Antonio Cancer Institute, University of Texas Health Science Center, San Antonio, TX, USA
PURPOSE: To report the long-term follow-up of Southwest Oncology Group-8269, a phase II North American cooperative group trial of concurrent cisplatin, etoposide, vincristine (PEV), and thoracic radiotherapy (TRT) for limited small-cell lung cancer (L-SCLC). METHODS: 114 eligible patients from 47 institutions enrolled between April, 1985 consisted of three cycles of PEV. TRT was administered at 1.8 Gy/fraction in 25 daily fractions to a total dose of 45 Gy, to begin concomitantly. Consolidative chemotherapy included two cycles of vincristine, methotrexate, etoposide, doxorubicin and cyclophosphamide. Prophylactic cranial irradiation (PCI) was concurrent with the 3rd cycle of chemotherapy. The PCI dose was 30 Gy in 15 fractions of 2 progression-free with a minimum follow-up interval of 13.2 years, as of patients died of causes other than SCLC and five patients are still alive and progression-free. Of the remaining 71 patients dying of SCLC, local failure (LF) occurred in 24% (17 patients), distant metastasis (DM) occurred in 35% (25 patients), simultaneous LF and DM occurred in 25% (18 patients), and was indeterminate in 16% (11 patients). Thus, LF was a component of failure in 49%. Twenty patients had the CNS as the initial site of failure. Eleven patients (10%) developed fatal second primary cancers, including two with acute myelogenous leukemia, two with squamous cell lung cancer, one each with breast, pancreas, prostate, renal cell, and myelodysplasia. One patient developed both a melanoma and non-Hodgkin's lymphoma. CONCLUSION: There are long-term survivors with concomitant TRT and PEV. LF and DM are common. Pattern of failure suggests needs to improve local and systemic control.
UI - 21436114
AU - Miller AA; Niell HB
TI - Phase I and pharmacologic study of sequential topotecan, carboplatin, and etoposide.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):241-8
AD - Veterans Affairs Medical Center- Memphis, 1030 Jefferson Avenue, Memphis, TN 38104, USA. firstname.lastname@example.org
Inhibition of topoisomerase I by topotecan results in a compensatory increase in topoisomerase II levels associated with increased in vitro sensitivity of tumors to etoposide. Maximum synergy has been observed for the sequence of topotecan followed by etoposide. This is the pharmacologic rationale for the sequence of topotecan 0.4 mg/m(2) per day for 7 days continuous i.v. infusion, carboplatin i.v. on day 8, and etoposide 50 mg per day p.o. days 9 through 20. The carboplatin dosage was escalated from an AUC of 4 to 5 to 6 (Calvert formula). Up to six treatment cycles were administered at 28-day intervals. Eligible patients had metastatic non-small cell lung cancer (NSCLC) or extensive disease small lung cell lung cancer (SCLC), no prior chemotherapy, performance status 0-2, and adequate organ function. Follow-up was twice weekly in the first cycle for CBC and for topotecan and etoposide concentrations. Follow-up, thereafter, was weekly. Tumor response was assessed after two and six cycles and then as clinically indicated. At carboplatin AUCs of 4 and 5, no NCI grade 4 toxicity was observed in cycle 1 in cohorts of three patients each. At the AUC of 5, two patients experienced dose-limiting events after cycle 3, one grade 4 neutropenia lasting >3 days (no fever) and one failure to recover an absolute neutrophil count >1500/microl by day 35. This was, therefore, deemed the maximal tolerable dose. Number of treatment cycles per patient ranged between 1 and 6, and three patients completed six cycles. All patients were male, age 47-71, with NSCLC in one and SCLC in six. The patient with NSCLC had progressive disease after one cycle. One complete and three partial responses were observed in five patients with SCLC. Mean steady-state plasma concentrations during topotecan infusion ranged from 0.73 to 1.69 ng/ml, and mean etoposide concentrations ranged from 60 to 230 ng/ml. This sequence of topotecan, carboplatin, and etoposide appeared tolerable and active. Neutropenia was the dose-limiting toxicity.
UI - 21436115
AU - Videtic GM; Fung K; Tomiak AT; Stitt LW; Dar AR; Truong PT; Yu EW;
TI - Vincent MD; Kocha WI Using treatment interruptions to palliate the toxicity from concurrent chemoradiation for limited small cell lung cancer decreases survival and disease control.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):249-58
AD - The Department of Radiation Oncology, London Regional Cancer Center, University of Western Ontario, London, Ontario, Canada. email@example.com
BACKGROUND AND PURPOSE: We analyzed the impact on survival outcomes of treatment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radiotherapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years. MATERIALS AND METHODS: From 1989 to 1999, 215 patients received treatment for LSCLC, consisting of six cycles of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine (CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, delivered to a target volume encompassing gross disease and suspected microscopic disease with a 2 cm margin. Treatment breaks arising during concurrent ChT+RT were used to manage severe symptomatic or hematologic toxicities. We used the interruptions in thoracic RT as the 'marker' for any concurrent break and measured 'break duration' by the total length of time (in days) RT was interrupted, since that also signaled that ChT could be re-initiated. Patient results were analyzed for the impact of interruptions/treatment prolongation on overall and disease-free survival. RESULTS: For all patients, 2-year and 5-year overall and disease-specific survivals were 22.7 and 7.2, 27.6 and 9.3%, respectively; overall and disease-specific median survivals were 14.7 months each. A total of 56 patients (26%) had treatment breaks due to toxicity. Hematologic depression caused the majority of breaks (88%). The median duration of breaks was 5 days (range 1-18). Patients with and without interruptions were compared for a range of prognostic factors and were not found to have any significant differences. Comparing interrupted/uninterrupted courses, median survivals were 13.8 versus 15.6 months, respectively, and 5-year overall survivals were 4.2 versus 8.3%, respectively. There was a statistical difference between overall survival curves which favored the uninterrupted group (P=0.01). When comparing a series of prognostic variables, multivariable analysis found that the most significant factor influencing survival in the present study was the presence of treatment breaks (P=0.006). There was a trend for development of any recurrence in the patients with breaks (P=0.08). When controlling for the use of prophylactic cranial irradiation (PCI) in the two groups, the rate of failure in the chest was higher in the patients with RT breaks (58 vs. 33%). The rate of failure in the brain was dependent on the use of PCI only. CONCLUSIONS: Interruptions in treatment to palliate the toxicity from concurrent chemoradiation result in poorer local control and decreased survival.
UI - 21436116
AU - Kunitoh H; Akiyama Y; Kusaba H; Yamamoto N; Sekine I; Ohe Y; Kubota K;
TI - Tamura T; Shinkai T; Kodama T; Goto K; Niho S; Nishiwaki Y; Saijo N A phase I/II trial of cisplatin, docetaxel and ifosfamide in advanced or recurrent non-small cell lung cancer.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):259-65
AD - Department of Medical Oncology, National Cancer Center Hospital: 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. firstname.lastname@example.org
This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.
UI - 21436117
AU - Huisman C; Giaccone G; van Groeningen CJ; Sutedja G; Postmus PE; Smit EF
TI - Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):267-75
AD - Department of Pulmonary Diseases, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
BACKGROUND: Many regimens of gemcitabine-cisplatin chemotherapy have proven activity in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal dose and schedule still have to be established. PATIENTS AND METHODS: We conducted a phase II study with administration of cisplatin 50 mg/m(2) on days 1 and 8 and gemcitabine 800 mg/m(2) on days 2, 9 and 15. This schedule was selected to optimise the synergism between the two drugs and reduce toxicity due to high dose cisplatin. RESULTS: Thirty-six chemo-naive patients with stage IIIA, IIIB or IV NSCLC entered the study (26 men, 10 women; median age 58 years, range 29-74). Twenty patients achieved a partial response: 7 out of 10 stage IIIA patients, 7 out of 13 stage IIIB patients and 6 out of 13 stage IV patients. On intent-to-treat basis, the overall response rate (RR) was 58% (95% confidence interval, 42-74%). Ninety percent of stage IIIA patients and 46% of stage IIIB patients received adjuvant surgery or radiotherapy. Overall median duration of response was 28 weeks (range 6-147 weeks). For stage IIIA, IIIB and IV patients, these numbers were 91, 13 and 23 weeks, respectively. One-year survival was 49% with 90%, 23% and 42% for stage IIIA, IIIB and IV patients, respectively. The main toxicity was myelosuppression. WHO grades 3 and 4 leukopenia occurred in 67% of patients, whereas 61% experienced grade 3 or 4 thrombocytopenia. Although hematological toxicity was clinically tolerable, it frequently led to omission of gemcitabine administration on day 15. The incidence of non-hematological toxicity was very low. CONCLUSION: This regimen of cisplatin on days 1 and 8 and gemcitabine on days 2, 9 and 15 induced a high RR in patients with advanced NCSLC. Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination.
UI - 21436118
AU - Rebattu P; Quantin X; Ardiet C; Morere JF; Azarian MR; Schuller-Lebeau
TI - MP; Pujol JL Dose-finding, pharmacokinetic and phase II study of docetaxel in combination with gemcitabine in patients with inoperable non-small cell lung cancer.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):277-87
AD - Cancer Institute Centre Leon Berard 28, rue Laennec, 69373 Lyon, Cedex, France. email@example.com
BACKGROUND: The good efficacy-toxicity ratio of both docetaxel and gemcitabine in non-small cell lung cancer (NSCLC) stimulates the investigation of the combination of these drugs as a first line chemotherapy. This two-step study firstly aimed at determining the maximum tolerated and recommended doses of docetaxel given every 3 weeks in combination with a fixed dose of gemcitabine; the phase I study paid particular attention to pharmacokinetics. Afterwards, the safety and efficacy of the recommended dose was carefully assessed in the phase II-step. METHODS: The following range of docetaxel dosages were tested in the phase I study; 60, 75, 85, and 100 mg m(-2) given on day 8 in combination with gemcitabine 1000 mg m(-2) delivered on days 1 and 8 of a 3-week cycle. Haematopoietic growth factors were not allowed. The treatment was delivered on an outpatient basis. Main eligibility criteria consisted of stage III b or IV histologically proven NSCLC, Eastern Co-operative Oncology Group (ECOG) performance status PS < or =2, age < or =70 years, measurable disease, adequate blood counts, chemistry, and no symptomatic brain metastasis. RESULTS: Four centres enrolled 49 patients (eight having been pre-treated); 16 in phase I and 33 in phase II. The maximal tolerated dose was almost reached at the last dose level (i.e. docetaxel, 100 mg m(-2)). Consequently, we considered the 85 mg m(-2) level as the recommended dose. There was a positive relationship of the docetaxel dose to the area under the curve of this drug. Toxicity was assessable in all patients. Among the 200 cycles delivered, 192 were assessable for this feature. Main toxicity was grade 3-4 neutropenia affecting 23 patients (47% of the population; 23% of the cycles). Six febrile episodes were recorded leading to two treatment-related deaths. Another patient died from congestive cardiac failure. In addition, six patients experienced interstitial pneumonitis, (one half considered as severe), two of them having received the recommended dose. All patients recovered from this toxicity after corticosteroids. Fourteen patients out of the whole population (29%; 95% CI [17-43], including ten patients receiving the recommended dose), achieved an objective response. Median follow-up was 14 months (range, 0.3-29.4). Median survival was 11.2 months (95% CI [8.3-13.2]), and the 1-year survival rate was 45%. CONCLUSION: Gemcitabine, 1000 mg m(-2) days 1 and 8 in combination with docetaxel, 85 mg m(-2), day 8, given every 3 weeks could be considered as an active regimen with manageable toxicities in locally advanced or metastatic NSCLC. This study deserves further comparisons with classical platinum-based regimens.
UI - 21436119
AU - van Putten JW; Baas P; Codrington H; Kwa HB; Muller M; Aaronson N; Groen
TI - HJ Activity of single-agent gemcitabine as second-line treatment after previous chemotherapy or radiotherapy in advanced non-small-cell lung cancer.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):289-98
AD - Department of Pulmonary Diseases, University Hospital, Groningen, The Netherlands. firstname.lastname@example.org
The aim of the study was to evaluate activity, toxicity and health-related quality of life (HRQL) with gemcitabine as second-line treatment after previous chemo- or radiotherapy in non-small-cell lung cancer (NSCLC). Patients with previously treated NSCLC were treated with gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 in a 28-day cycle. Eighty patients were included; median age was 57 years (range 38-77). Prior treatment consisted of platinum-containing chemotherapy in 29 patients and high-dose thoracic radiotherapy in 51 patients. Median number of cycles was three (range 1-6). Granulocytopenia CTC grade 3 and 4 occurred in 9% and thrombocytopenia CTC grade 3 and 4 in 9% of cycles. Non-haematological toxicity was mild. Tumour response was achieved in 13% of the patients (95% CI 7-20), median survival time was 26 weeks and 1-year survival was 22%. Tumour response to second-line gemcitabine could not be predicted from response to first-line therapy, first-line treatment modality or treatment interval. In a subset of 35 patients HRQL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 questionnaires and showed improvement or control of symptoms and functioning in approximately 30% of patients. We conclude that gemcitabine in second-line treatment has modest anti-tumour activity, is well tolerated, and may control tumour-related symptoms and improve HRQL in a significant minority of patients.
UI - 21455235
AU - Iyoda A; Hiroshima K; Toyozaki T; Haga Y; Baba M; Fujisawa T; Ohwada H
TI - Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features.
SO - Cancer 2001 Sep 1;92(5):1108-12
AD - Division of Pathology, Institute of Pulmonary Cancer Research, Chiba University School of Medicine, Chiba, Japan. email@example.com
BACKGROUND: In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma, large cell carcinoma with neuroendocrine differentiation, and large cell carcinoma with neuroendocrine morphology as a variant of large cell carcinoma. Patients with large cell carcinoma with neuroendocrine features have poor prognoses, comparable to those for small cell lung carcinoma. Small cell lung carcinoma is sensitive to chemotherapy; however, it is still unclear whether large cell carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. METHODS: The authors analyzed 73 patients with large cell carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. RESULTS: In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small cell lung carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with large cell carcinoma with neuroendocrine features in early stage. Copyright 2001 American Cancer Society.
UI - 21455248
AU - Socinski MA; Rosenman JG; Halle J; Schell MJ; Lin Y; Russo S; Rivera MP;
TI - Clark J; Limentani S; Fraser R; Mitchell W; Detterbeck FC Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified phase I/II trial.
SO - Cancer 2001 Sep 1;92(5):1213-23
AD - Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA. firstname.lastname@example.org
BACKGROUND: A modified Phase I/II trial was conducted evaluating the incorporation of three-dimensional conformal radiation therapy into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III unresectable nonsmall cell lung carcinoma (NSCLC). The dose of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints included response rate, toxicity, and survival. METHODS: Sixty-two patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (area under the concentration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x 6) carboplatin (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS: The response rate to induction carboplatin/paclitaxel was 40%. Eight patients (13%) progressed on the induction phase. No dose-limiting toxicity was observed during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, however, only 8% developed Grade 3/4 esophagitis using Radiation Therapy Oncology Group criteria. The overall response rate was 52%. Survival rates at 1, 2, 3, and 4 years were 71%, 52%, 40%, and 36%, respectively, with a median survival of 26 months. The 1-, 2-, and 3-year progression free survival probabilities were 47%, 35%, and 29%, respectively. CONCLUSIONS: Incorporation of TCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Both locoregional and distant failure remain problematic in this population of patients. Copyright 2001 American Cancer Society.
UI - 21468603
AU - Thomas AL; Cox G; Sharma RA; Steward WP; Shields F; Jeyapalan K; Muller
TI - S; O'Byrne KJ Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.
SO - Eur J Cancer 2000 Dec;36(18):2329-34
AD - Department of Oncology, Leicester Royal Infirmary, UK.
The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.
UI - 21262958
AU - Tsavaris N; Kosmas CH; Vadiaka M; Kontos A; Katsorida M; Dimitrakopoulos
TI - A; Zerai A; Koufos CH Efficacy of ondansentron treatment for acute emesis with different dosing schedules 8 vs 32 mg. A randomized study.
SO - J Exp Clin Cancer Res 2001 Mar;20(1):29-34
AD - Dept. of Pathophysiology, University of Athens, School of Medicine, Laiko Hospital, Greece.
The aim of the present randomized study was to evaluate which dose of Ondansentron (OND)(32 versus 8 mg) is appropriate for the antiemetic treatment of a uniform group of patients (pts) with Non Small Cell Lung Cancer (NSCLC) who were treated with Cisplatin (CDDP) 100 mg/m2 in combination with other less emetogenic drugs. One hundred and ten patients, with histologically confirmed NSCLC entered this randomized study. They were between 50 - 70 years old, with no previous Chemotherapy, with a PS (Karnofsky) >60%. They were randomized into two groups; Group A: OND as a 32 mg dose the first 24 hours, followed by 8 mg every 8 hrs for the following four days, combined with dexamethasone, 8 mg i.v. the first day, and 8 mg p.o., in the morning, the following three days. Group B: OND as a 8 mg dose every day for 4 days, combined with dexamethasone 8 mg i.v. and 8 mg p.o. the following three days. In this randomized study, of the 110 patients who entered, 106 were evaluable. Clinical parameters were similar between the examined groups. A higher number of patients of Group A presented complete response (P 0.0001), compared to patients of Group B who failed (P 0.004), during the first 24 hours. In the 3 days that followed, a higher number of pts of Group A presented complete response to the antiemetic therapy (P 0.001, P 0.0001), while Group B failed (P 0.007, P 0.001, P 0.019), or presented minor response (P 0.0001, P 0.004). Patients who had no antiemetic response needed additional therapy and were excluded from the evaluatio (13 pts of Group B). Retches (P 0.0001, P 0.005), and nausea (P 0.0001, P were also frequent in Group B. We concluded that reduced OND doses (8 mg) are inadequate in the prevention of emesis after high dose CDDP (100 mg/m2) and should be avoided.
UI - 21289709
AU - Rojanasthien N; Kumsorn B; Atikachai B; Leotrakul S; Thongprasert S
TI - Protective effects of fosfomycin on cisplatin-induced nephrotoxicity in patients with lung cancer.
SO - Int J Clin Pharmacol Ther 2001 Mar;39(3):121-5
AD - Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand. email@example.com
SUBJECTS, MATERIAL AND METHODS: Protective effects of fosfomycin on cisplatin-induced nephrotoxicity have been previously reported, however, the proper time, duration and dosage of its administration were uncertain. Therefore, we investigated the protective effect of concurrent administration of twice-daily doses of 2 g fosfomycin for 5 days in 13 cisplatin-naive lung cancer patients who were due to receive a single dose per cycle of 100 mg/m2 cisplatin. On each chemotherapeutic cycle, patients were randomly given cisplatin alone or cisplatin plus fosfomycin every 4 weeks for a maximum of 4 consecutive cycles. Indicators of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, serum creatinine (Scr) and creatinine clearance (Clcr) were determined the day before and at day 3 and day 6 after cisplatin administration. Results were compared and statistically analyzed by the non-parametric Mann-Whitney's test. We found that the NAG activities obtained on day 0, day 3 and day 6 of the fosfomycin cycles were comparable to values obtained during the control cycles (p > 0.05). Moreover, the NAG activities on day 3 of both treatment cycles were significantly elevated from baseline (p < 0.01) and had normalized on day 6. There were no significant changes in serum creatinine and creatinine clearance. CONCLUSION: High-dose cisplatin induced reversible elevation of urinary NAG and concurrent administration of low-dose fosfomycin for 5 days had no effect on the enzymuria. In the prevention of cisplatin nephrotoxicity, a further study using dose escalation (8 to 12 g/d) of fosfomycin administered 2 to 3 days prior to cisplatin are required to demonstrate its nephroprotective effects.
UI - 21413473
AU - Lee HZ
TI - Effects and mechanisms of emodin on cell death in human lung squamous cell carcinoma.
SO - Br J Pharmacol 2001 Sep;134(1):11-20
AD - School of Pharmacy, China Medical College, 91, Hsueh-Shih Road, Taichung, 404, Taiwan.
1. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component from the root and rhizome of Rheum palmatum that has been reported to exhibit antitumour effects, but the mechanism is not known. The study investigated the effects and mechanisms of emodin-induced cell death in human lung squamous carcinoma cell line CH27. 2. Emodin (50 microM)-induced CH27 cell apoptosis was confirmed by cell morphological change, sub-G1 formation in flow cytometry analysis, viability assay and degradation of focal adhesion kinase in this study. 3. Emodin-induced apoptosis of CH27 cells does not involve modulation of endogenous Bcl-X(L) protein expression, but appears to be associated with the increased expression of cellular Bak and Bax proteins. This study also demonstrated the translocation of Bak and Bax from cytosolic to particulate fractions. 4. This study has shown that emodin-treated CH27 cells revealed the increases in the relative abundance of cytochrome c for the indicated time intervals in cytosolic fraction. 5. This study demonstrates that the activation of caspase-3, caspase-9 and caspase-8 is an important determinant of apoptotic death induced by emodin. 6. These results suggested that emodin induces CH27 cell death by Bax death pathway and Fas pathway.
UI - 21453152
AU - Hirota S; Tsujino K; Endo M; Kotani Y; Satouchi M; Kado T; Hishikawa Y;
TI - Obayashi K; Takada Y; Kono M; Abe M Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Oct 1;51(2):291-5
AD - Department of Radiology, Hyogo Medical Center for Adults, Akashi, Japan. firstname.lastname@example.org
PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS: All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.
UI - 21381728
AU - Kelly K; Lovato L; Bunn PA Jr; Livingston RB; Zangmeister J; Taylor SA;
TI - Roychowdhury D; Crowley JJ; Gandara DR; Southwest Oncology Group Cisplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in untreated patients with extensive-stage small cell lung cancer: a phase II trial of the Southwest Oncology Group.
SO - Clin Cancer Res 2001 Aug;7(8):2325-9
AD - University of Colorado, Denver, CO 80262, USA.
PURPOSE: This study was designed to determine the efficacy and toxicity of cisplatin, etoposide, and paclitaxel (PET) in patients with extensive-stage small cell lung cancer (ES-SCLC). EXPERIMENTAL DESIGN: Chemo-naive adult patients with a performance status (PS) of 0-2 and adequate organ function were eligible. Patients received cisplatin 80 mg/m(2) i.v., etoposide 80 mg/m-2 i.v., and paclitaxel 175 mg/m(2) i.v. over a 3-h period on day 1 followed by etoposide 160 mg/m(2) p.o. on days 2 and 3 every 21 days for six cycles. G-CSF 5 microg/kg was injected s.c. on days 4-14. RESULTS: Eighty-eight patients were assessable. The median age was 60 years; 50% were male, 78% had PS of 0-1, 28% had PS of 2, 53% had multiple sites, and 13% had brain involvement. The overall response rate was 57% with 10 (12%) of 84 patients achieving a complete response. Median progression-free survival was 6 months [95% confidence interval (CI), 5-7 months] with a median survival of 11 months (95% CI, 8-13 months) and a 1-year survival rate of 43% (95% CI, 33-54%). Six patients (7%) died from toxicity. Grade 5 toxicity occurred in 3 (14%) of 22 patients (with a PS of 2) versus 3 (5%) of 61 patients (with a PS of 0-1; P, not significant). Grade 4 neutropenia developed in 40% of patients. Grade 3 nonhematological toxicities were primarily nausea (20%), vomiting (16%), and fatigue (14%). CONCLUSION: The survival result achieved was superior to prior SWOG experiences; however, the toxic death rate was unacceptably high in PS-2 patients. These results provide the largest database for the ongoing randomized Intergroup trial comparing PET to cisplatin+etoposide in PS-0-1 patients with ES-SCLC.
UI - 21466980
AU - Zwitter M; Cufer T; Wein W
TI - Gemcitabine and vincristine: an effective outpatient regimen with low myelotoxicity for stage IV non-small cell lung cancer.
SO - Neoplasma 2001;48(3):200-2
AD - Institute of Oncology, Zaloska, Ljubljana, Slovenia. email@example.com
The activity and tolerability of gemcitabine and the non-overlapping toxicity of gemcitabine plus vincristine were the basis for testing this regimen patients with non-small cell lung cancer (NSCLC). Forty patients (25 male/15 female, median age 52 years) with stage IV NSCLC and a Karnofsky Performance Status score > or = 60 entered the trial. Patients received gemcitabine 1000 mg/m2 on days 1, 8 and 15 and vincristine 1.4 mg/m2 on days 1 and 15, every 4 weeks. The overall response rate was 16/40 (40%) (N = 40); with 2 complete and 14 partial responses; additional 14 patients had minor responses or stable disease. Median duration of remission was 4.5 months, and the median survival was 9 months. In two patients with grade 2 generalized vesicular rash and severe malaise, respectively, treatment-related toxicity led to early termination of treatment. Among patients treated for more than two months, vincristine doses were reduced/omitted for 55% of cycles because of grade 1-2 peripheral neuropathy. Myelotoxicity was frequent but rarely clinically significant. Mean platelet counts on day 1 of cycles 2,3 and 4 were significantly higher than the pre-treatment or post-treatment values. We conclude that vincristine plus gemcitabine is an an active and well tolerated regimen. Its interesting "platelet-saving" effect deserves further investigation.
UI - 21468734
AU - Choy H; Pyo H; Kim JS; MacRae R
TI - Role of taxanes in the combined modality treatment of patients with locally advanced non-small cell lung cancer.
SO - Expert Opin Pharmacother 2001 Jun;2(6):963-74
AD - Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-5671, USA. firstname.lastname@example.org
The plant-derived taxanes have a unique mechanism of cytotoxic action and have shown interesting response and survival data in metastatic non-small cell lung cancer (NSCLC). Based on these results, taxane-based regimens have been investigated in combination with radiotherapy in unresectable NSCLC. Trials with paclitaxel-based concurrent chemoradiotherapy have shown 50-100% tumour response rates, 12-26 month median survivals and 32-52% 2-year survival rates. Trials with concurrent chemoradiotherapy with docetaxel have shown 35-92% tumour response rates, 12-23 month median survivals, and 41-43% 2 year survival rates. Taxane-based concurrent chemoradiotherapy for stage III NSCLC appears promising. Large ongoing randomised trials will define the role of these agents in the treatment of locally advanced NSCLC.
UI - 21491127
AU - Chang AY; Rubins J; Asbury R; Boros L; Hui LF
TI - Weekly paclitaxel in advanced non-small cell lung cancer.
SO - Semin Oncol 2001 Aug;28(4 Suppl 14):10-3
AD - Johns Hopkins Singapore Clinical Services, Singapore.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most commonly used agents in treating patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). It is usually given once every 3 weeks. We have evaluated paclitaxel given once per week for 3 weeks every 4 weeks for patients with recurrent or metastatic NSCLC. Two consecutive studies using weekly paclitaxel were performed. The first study was a dose-escalation study with paclitaxel beginning at 50 mg/m(2) days 1, 8, and 15 every 4 weeks. Subsequent dose escalation was performed with 10 mg/m(2) increments per week. The second phase II study used paclitaxel at 80 mg/m(2) days 1, 8, and 15 every 4 weeks. The phase I study showed that the maximum tolerated dose was 90 mg/m(2)/wk for 3 weeks with 1 week off. The efficacy and side effects of both phase I and II were quite similar; therefore, the results were combined. Seventeen patients were in the phase I and 30 patients in the phase II study. The mean age was 72 years. Twenty-three patients had Eastern Cooperative Oncology Group performance status of 2 and 16 patients had received prior chemotherapy. One complete and 13 partial responses were observed with response duration ranging from 1 to 18+ months. Overall response rate was 30% (95% confidence interval, 18.5% to 42%). Overall median survival was 184 days. Grade 3/4 neutropenia was 8.5%, grade 3/4 infections was 6.4%, and grade 2 peripheral neuropathy was also 6.4%. Hyperglycemia with random blood sugar levels greater than 250 mg/dL was 6.4% and grade 3 fatigue was 4.3%. In general, treatment was well tolerated. In the best prognostic group of 16 patients without prior chemotherapy and with performance status 0 to 1, the response rate was 37.5% with a 1-year survival rate of 44% and median survival of 305 days. Prior chemotherapy, poor performance status, age higher than 70 years, and male gender carried a worse prognosis. In both phase I and II studies we observed limited myelosuppression, peripheral neuropathy, and constitutional symptoms. Weekly paclitaxel, delivered at our schedule, is an active and well-tolerated regimen. The role of weekly paclitaxel in NSCLC should be better defined in future randomized studies. Copyright 2001 by W.B. Saunders Company.
UI - 21491128
AU - Belani CP
TI - Interim analysis of a phase II study of induction weekly paclitaxel/carboplatin regimens followed by maintenance weekly paclitaxel for advanced and metastatic non-small cell lung cancer.
SO - Semin Oncol 2001 Aug;28(4 Suppl 14):14-6
AD - University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
This multi-institutional randomized phase II study was designed to compare the efficacy and toxicity of three different weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin schedules in patients with advanced and metastatic non-small cell lung cancer. The second part of the trial evaluated the role of maintenance weekly paclitaxel for those with response or stable disease after 16 weeks of initial treatment. Patients in arm 1 received paclitaxel 100 mg/m(2)/wk for 3 weeks along with carboplatin (area under the curve of 6) on day 1 every 4 weeks. The treatment in arm 2 was the same as in arm 1 except that carboplatin was also administered weekly (area under the curve of 2) for 3 weeks. Patients in arm 3 received paclitaxel 150 mg/m(2)/wk and carboplatin (area under the curve of 2 per week) during the second 8-week cycle. The total duration of this initial therapy was 16 weeks. All regimens were well tolerated. Arm 1 has the best therapeutic index and will exceed the median survival seen in previous phase III trials with traditional schedules of paclitaxel and carboplatin. Copyright 2001 by W.B. Saunders Company.
UI - 21491129
AU - Choy H; MacRae R
TI - The current state of paclitaxel and radiation in the combined-modality therapy of non-small cell lung cancer.
SO - Semin Oncol 2001 Aug;28(4 Suppl 14):17-22
AD - Center for Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232-5671, USA.
The results of randomized trials have prompted an evolution in the treatment approach to inoperable locally advanced non-small cell lung cancer, from radiotherapy alone to sequential chemoradiotherapy and now to concurrent chemoradiotherapy. The improvement in outcome seen with a concurrent chemoradiotherapy approach may be because of spatial cooperation, enhanced radiosensitization, and/or enhanced cytotoxicity. The taxanes, specifically paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), delivered in combination with radiation have been extensively examined in both preclinical and clinical studies. Several mechanisms have been suggested to explain the enhanced tumor cell kill seen with paclitaxel and radiation, and phase II studies have examined this combination in the setting of inoperable stage III non-small cell lung cancer. This review will explore some of the studies with this treatment approach in locally advanced disease. We also will briefly discuss some of the ongoing trials that are attempting to refine the delivery of concurrent thoracic radiation and paclitaxel-based chemotherapy. Copyright 2001 by W.B. Saunders Company.
UI - 21491131
AU - Depierre A; Westeel V
TI - Overview of the role of neoadjuvant chemotherapy for early stage non-small cell lung cancer.
SO - Semin Oncol 2001 Aug;28(4 Suppl 14):29-36
AD - Department of Pneumology, University Hospital, Besancon, France.
Preoperative chemotherapy has been intensively studied in stage IIIA non-small cell lung cancer and, to a lesser extent, in stage IIIB. For a considerable time period, early stage non-small cell lung cancer was dropped from studies. For early investigators, shrinking the tumor size, thus allowing complete resection of initially unresectable tumors, appeared as important as destroying micrometastases. Nevertheless, analysis of relapse patterns shows that preoperative chemotherapy appears to act more on micrometastases than on local control. The first randomized studies of preoperative chemotherapy were conducted only among patients with stage IIIA disease. The French Cooperative Oncology Group presented a large randomized study among 373 stage IB, II, and IIIA patients at the American