National Cancer Institute®
Last Modified: January 1, 2002
UI - 10735887
AU - Kaufmann M; Bajetta E; Dirix LY; Fein LE; Jones SE; Zilembo N; Dugardyn
TI - JL; Nasurdi C; Mennel RG; Cervek J; Fowst C; Polli A; di Salle E; Arkhipov A; Piscitelli G; Miller LL; Massimini G Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. The Exemestane Study Group.
SO - J Clin Oncol 2000 Apr;18(7):1399-411
AD - Universitatsklinik, Frankfurt, Germany.
PURPOSE: This phase III, double-blind, randomized, multicenter study evaluated the efficacy, pharmacodynamics, and safety of the oral aromatase inactivator exemestane (EXE) versus megestrol acetate (MA) in postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen. PATIENTS AND METHODS: A total of 769 patients were randomized to EXE 25 mg/d (n = 366) or MA (n = 403) 40 mg four times daily. Tumor response, duration of tumor control, tumor-related signs and symptoms (TRSS), quality of life (QOL), survival, and tolerability were evaluated. RESULTS: Overall objective response (OR) rates were higher in patients treated with EXE than in those treated with MA (15.0% v 12.4%); a similar trend was noted in patients with visceral metastases (13.5% v 10.5%). Median survival time was significantly longer with EXE (median not reached) than with MA (123.4 weeks; P =.039), as were the median duration of overall success (OR or stable disease > or = 24 weeks; 60.1 v 49.1 weeks; P =.025), time to tumor progression (20.3 v 16.6 weeks; P =.037), and time to treatment failure (16.3 v 15.7 weeks; P =.042). Compared with MA, there were similar or greater improvements in pain, TRSS, and QOL with EXE. Both drugs were well tolerated. Grade 3 or 4 weight changes were more common with MA (17.1% v 7.6%; P =.001). CONCLUSION: EXE prolongs survival time, time to tumor progression, and time to treatment failure compared with MA and offers a well-tolerated treatment option for postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen.
UI - 10920131
AU - Chaplain G; Milan C; Sgro C; Carli PM; Bonithon-Kopp C
TI - Increased risk of acute leukemia after adjuvant chemotherapy for breast cancer: a population-based study.
SO - J Clin Oncol 2000 Aug;18(15):2836-42
AD - Registre des Cancers Gynecologiques de Cote d'Or, Faculte de Medecine, Dijon, France.
PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors. PATIENTS AND METHODS: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Cote d'Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area. RESULTS: Until leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P <.0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses >/= 13 mg/m(2). CONCLUSION: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.
UI - 11148553
AU - Allison R; Mang T; Hewson G; Snider W; Dougherty D
TI - Photodynamic therapy for chest wall progression from breast carcinoma is an underutilized treatment modality.
SO - Cancer 2001 Jan 1;91(1):1-8
AD - Department of Photodynamic Therapy, Buffalo General Hospital, Buffalo, New York, USA.
BACKGROUND: Chest wall progression of breast carcinoma after failure of salvage surgery, radiation, and chemohormonal therapy is a quagmire with limited therapeutic options. Because photodynamic therapy (PDT) offers excellent results in cutaneous lesions, PDT may play a role in this indication. However, to the authors' knowledge, published data for this subgroup of patients using the only commercially available photosensitizing agent, Photofrin, often show high treatment morbidity, limiting PDT's usefulness. The authors report the feasibility of decreasing the photosensitizer drug dose as a means of exploiting photobleaching kinetics to improve the therapeutic ratio for these individuals. METHODS: One hundred two chest wall sites were treated with PDT after failure of multimodality salvage therapy. In these 9 patients, lesion size ranged from 0.57 to 9 cm. Photodynamic therapy consisted of outpatient intravenous infusion of 0.8 mg/kg of Photofrin, followed 48 hours later by 630 nm light treatment of 135-170 J/cm2 delivered by a KTP:YAG laser coupled to dye unit. Two patients underwent a second PDT procedure due to new lesion formation. All patients were observed for a minimum of 6 months, and none was lost to follow-up. RESULTS: Photodynamic therapy was well tolerated with no photosensitivity reported. Despite all patients having failed surgery, full dose radiation and multiagent chemohormonal therapy, chest wall lesions healed with no scarring. Only 1 (9 cm) lesion took longer than 3 months to granulate over. The authors were able to evaluate all treatment sites, and complete response, defined as total lesion elimination, was noted in 89% of the lesions; reduction without regrowth occurred in 8% with no response in 3% of the lesions. CONCLUSIONS: Despite having prior treatment and fragile tissues, low dose Photofrin-induced PDT offers excellent clinical response with minimal morbidity. These results show that PDT should play an important role in the management of chest wall failure from breast carcinoma. Copyright 2001 American Cancer Society.
UI - 11410835
AU - Nguyen MC; Stewart RB; Banerji MA; Gordon DH; Kral JG
TI - Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer.
SO - Int J Obes Relat Metab Disord 2001 Feb;25(2):296-8
AD - Department of Surgery, SUNY Downstate Medical Center, Brooklyn, New York 11203-2098, USA.
Tamoxifen is a nonsteroidal anti-estrogenic drug used for adjuvant treatment of breast cancer and recently as a chemopreventative agent for breast cancer and, on an investigational basis, for other cancers. To date there are case reports of hypertriglyceridemia and fatty liver disease in tamoxifen users. Fatty liver is associated with visceral obesity and other components of the metabolic syndrome. Here we evaluated steatosis and adipose tissue distribution by CT scan in a cross-sectional study of 32 women on tamoxifen and 39 control women. Tamoxifen users had more visceral adipose tissue (VAT) and more liver fat than controls. This is the first study to demonstrate that fatty liver and intra-abdominal fat accumulation are common in breast cancer patients receiving tamoxifen. Prospective studies of tamoxifen should monitor metabolic changes in obese women with or without breast cancer.
UI - 11370490
AU - Mendenhall NP
TI - Breast-conserving therapy for early-stage breast cancer.
SO - Hematol Oncol Clin North Am 2001 Apr;15(2):219-42
AD - Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida, USA. firstname.lastname@example.org
In most other organs (extremities, bladder, rectum, larynx, or eye), the acceptance of organ-conserving therapy into standard oncologic practice has required only the demonstration of feasibility and efficacy--not equivalency with the radical surgical alternative. BCT was not generally accepted as standard oncologic practice until the maturation of numerous prospective randomized trials that universally demonstrated equivalence in disease control outcomes and survival with mastectomy. In fact, the acceptance of BCT as standard therapy in many parts of the United States actually lagged more than a decade behind sentinel publications documenting proof of equivalency with mastectomy. Even today, investigators continue to search for a subset of breast cancer patients who will have better disease control with radical surgery. BCT stands as not only the best-studied example of organ-conserving therapy but one of the most rigorously tested therapies in all of medicine. Breast-conserving therapy requires a multidisciplinary approach with close coordination among team members from diagnosis through surveillance following treatment. The surgeon must be willing to assess and re-excise margins, to mark the tumor bed with clips, and to use sentinel node biopsy in appropriate patients. The radiation oncologist must be willing to use CT planning, paying close attention not only to coverage of target tissues but to avoidance of critical normal tissues. The medical oncologist must work closely with the surgeon and radiation oncologist to determine the optimal sequencing of therapies and selection of systemic agents. All must recognize special circumstances where genetic counselling may be beneficial, psychosocial support may be needed, or BCT may not be the best choice for patients. When used appropriately, BCT produces maximal disease control and quality of life while minimizing iatrogenic functional, cosmetic, and psychologic sequelae in patients with early-stage breast cancer. BCT serves as a model for the optimal combination of surgery and radiation in organ-preserving cancer therapy.
UI - 11417845
AU - Melichar B; Touskova M; Dvorak J; Jandik P; Kopecky O
TI - The peripheral blood leukocyte phenotype in patients with breast cancer: effect of doxorubicin/paclitaxel combination chemotherapy.
SO - Immunopharmacol Immunotoxicol 2001 May;23(2):163-73
AD - Department of Oncology & Radiotherapy, Charles University Medical School & Teaching Hospital, Hradec Kralove, Czech Republic.
Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3 HLA-DR+, CD3+CD69+ and CD14+CD16+, and significantly lower percentages of CD3 and CD8+CD28+ cells. After one cycle of AT, the absolute numbers of CD3 , CD3+CD4+, CD3+CD8+ and CD8+CD28+ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.
UI - 11432615
AU - Razis ED; Fountzilas G
TI - Paclitaxel: epirubicin in metastatic breast cancer--a review.
SO - Ann Oncol 2001 May;12(5):593-8
AD - 1st Department of Medical Oncology, Hygeia Hospital, Athens, Greece. email@example.com
BACKGROUND: Treatment of metastatic breast cancer (MBC) with paclitaxel (T) and doxorubicin has yielded high response rates but the regimen is associated with significant cardiac toxicity. Epirubicin (E) is a less cardiotoxic anthracycline which has also been combined with paclitaxel in the treatment of MBC. MATERIALS AND METHODS: This paper is a review of studies evaluating the pharmacokinetics, toxicity profile, and efficacy of the ET combination in MBC. RESULTS: The ET combination has been studied extensively in Europe. The unique pharmacokinetics of the combination do not lead to the accumulation of cardiotoxic metabolites as in the case of the doxorubicin-paclitaxel combination. In terms of efficacy, the ET combination yields an overall response rate of 50%-70% and complete response rate (CR) 10%-15% in MBC in the same range as the more recent doxorubicin paclitaxel studies. CONCLUSION: In summary the ET combination is safe and effective in MBC. It is less cardiotoxic than the doxorubicin paclitaxel combination. Further studies with ET in both the adjuvant setting and in MBC are in progress.
UI - 11432617
AU - Villalona-Calero MA; Blum JL; Jones SE; Diab S; Elledge R; Khoury P; Von
TI - Hoff D; Kraynak M; Moczygemba J; Kromelis P; Griffin T; Rowinsky EK A phase I and pharmacologic study of capecitabine and paclitaxel in breast cancer patients.
SO - Ann Oncol 2001 May;12(5):605-14
AD - Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, Texas, USA. firstname.lastname@example.org
BACKGROUND: Based on preclinical studies demonstrating that treatment with paclitaxel upregulates intratumoral thymidine phosphorylase (dTHdPase), which catalyzes the final step in the conversion of the oral fluoropyrimidine capecitabine to 5-fluorouracil (5-FU), as well as the overlapping spectra of activity for these agents, particularly in metastatic breast cancer, this phase I study evaluated the feasibility of administering capecitabine on an intermittent schedule in combination with paclitaxel in previously-treated patients with locally advanced or metastatic breast cancer. The study also sought to recommend doses for subsequent disease-specific studies, identify clinically significant pharmacokinetic interactions, and detect preliminary antitumor activity. PATIENTS AND METHODS: Nineteen previously treated women with metastatic breast cancer whose prior treatment included neither paclitaxel or capecitabine received one hundred one courses of capecitabine and paclitaxel. Paclitaxel was administered as a three-hour intravenous (i.v.) infusion at a fixed dose of 175 mg/m2 and capecitabine was administered as 2 divided daily doses for 14 days followed by a seven-day rest period every 3 weeks. The dose of capecitabine was increased from a starting dose of 1650 mg/m2/d. The plasma sampling scheme in the first course permitted characterization of the pharmacokinetics of each agent given alone and concurrently to detect major pharmacokinetic interactions. RESULTS: Palmar plantar erythrodysesthesia (hand foot syndrome) and neutropenia were the principal dose-limiting toxicities (DLT). Other toxicities included diarrhea and transient hyperbilirubinemia. Three of eight new patients treated with capecitabine 2000 mg/m2/d and paclitaxel 175 mg/m2 experienced DLT in the first course, whereas none of eleven new patients treated with capecitabine 1650 mg/m2/d and paclitaxel 175 mg/m2 developed DLT. Pharmacokinetic studies indicated that capecitabine did not grossly affect the pharmacokinetics of paclitaxel, and there were no major effects of paclitaxel on the pharmacokinetics of capecitabine and capecitabine metabolites. However, AUC values for the major 5-FU catabolite, fluorobeta-alanine (FBAL), were significantly lower in the presence of paclitaxel. Two complete and seven partial responses (56% response rate) were observed in sixteen patients with measurable disease; four of six patients whose disease was previously treated with high-dose chemotherapy and hematopoietic stem-cell support had major responses. Seven of nineteen patients had stable disease as their best response. CONCLUSIONS: Recommended combination doses of capecitabine on an intermittent schedule and paclitaxel are capecitabine 1650 mg/m2/d orally for 14 days and paclitaxel 175 mg/m2 i.v. every 3 weeks. The favorable preclinical interactions between capecitabine and paclitaxel, as well as the acceptable toxicity profile and antitumor activity in patients with metastatic breast cancer, support further clinical evaluations to determine an optimal role for the combination of capecitabine and paclitaxel in breast cancer and other relevant malignancies.
UI - 11432629
AU - Gazet JC; Ford HT; Gray R; McConkey C; Sutcliffe R; Quilliam J; Makinde
TI - V; Lowndes S; Coombes RC Estrogen-receptor-directed neoadjuvant therapy for breast cancer: results of a randomised trial using formestane and methotrexate, mitozantrone and mitomycin C (MMM) chemotherapy.
SO - Ann Oncol 2001 May;12(5):685-91
AD - Combined Breast Clinic, St. George's Hospital, London, UK.
BACKGROUND: We wanted to determine whether neoadjuvant systemic chemoendocrine therapy guided by the estrogen receptor (ER) status of the primary breast cancer, followed by conventional surgery and/or radiotherapy, reduces local and distant recurrence and improves survival compared with adjuvant treatment given conventionally postoperatively. PATIENTS AND METHODS: Two hundred ten patients with primary breast cancer (T1-T4, N0, N1-2) were randomised to receive treatment with neoadjuvant chemoendocrine therapy or conventional post-operative chemoendocrine therapy. Systemic therapy was based on the estrogen receptor (ER) status of the primary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m2), mitozantrone (7 mg/m2) and mitomycin (7 mg/m2) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post menopausal women formestane (250 mg every two weeks) over three months. RESULTS: With a minimum of five years follow-up, there is no evidence of any survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% +/- 4.7% (neoadjuvant) and 87% +/- 3.4% (adjuvant). Similarly, there was no apparent benefit in terms of disease-free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-responders (17 of 49; 35%) (P < 0.01). There was a reduction in the need for surgery in responding patients with T1 and T2 tumours, since 10 of 74 (14%) had no detectable residual tumour, without any apparent increase in the risk of local or distant recurrence. CONCLUSION: In this study neoadjuvant treatment with endocrine or chemotherapy provided no obvious survival benefit to women with breast cancer. However, it does allow avoidance of surgery in some cases. Also, the patients whose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tumours fail to respond.
UI - 11440031
AU - Tiling R; Linke R; Untch M; Richter A; Fieber S; Brinkbaumer K; Tatsch
TI - K; Hahn K 18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study.
SO - Eur J Nucl Med 2001 Jun;28(6):711-20
AD - Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Germany. email@example.com
Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUVmean, SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.
UI - 11456056
AU - Esserman L; Kaplan E; Partridge S; Tripathy D; Rugo H; Park J; Hwang S;
TI - Kuerer H; Sudilovsky D; Lu Y; Hylton N MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer.
SO - Ann Surg Oncol 2001 Jul;8(6):549-59
AD - Department of Surgery, University of California, San Francisco, USA. firstname.lastname@example.org
BACKGROUND: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy. METHODS: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI. RESULTS: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively. CONCLUSIONS: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.
UI - 11475386
AU - Jansen SJ; Kievit J; Nooij MA; Stiggelbout AM
TI - Stability of patients' preferences for chemotherapy: the impact of experience.
SO - Med Decis Making 2001 Jul-Aug;21(4):295-306
AD - Department of Clinical Oncology, Leiden University Medical Center, The Netherlands. S.J.T.Jansen.bsl@LUMC.nl
BACKGROUND: Studies have shown that utilities for a particular treatment, elicited by means of a hypothetical treatment scenario, may remain stable within the same patients when examined before, during, and after experiencing that treatment (within-group stability). However, other studies have found that utilities for a particular health state may differ between patient groups who are and who are not experiencing the particular health state (between-group differences). OBJECTIVE: The authors evaluated this apparent contradiction in the case of adjuvant chemotherapy for breast cancer. A related purpose was to examine whether a chemotherapy scenario adequately reflects the patients' own experiences with chemotherapy. METHOD: Forty-three patients with early-stage breast cancer evaluated their actually experienced health state and a chemotherapy scenario before, during, and after undergoing adjuvant chemotherapy (chemotherapy group). A control group of 51 patients for whom chemotherapy was not part of the treatment plan was interviewed at similar points in time. Utilities were elicited by means of a visual analog scale (VAS), a chained time trade-off (TTO), and a chained standard gamble (SG). RESULTS: The utilities for the chemotherapy scenario remained relatively stable over time in the 2 patient groups. Furthermore, the chemotherapy scenario was evaluated more positively by patients in the chemotherapy group than by control patients (e.g., utilities before chemotherapy: VAS 0.69 vs. 0.50, TTO 0.88 vs. 0.50, SG 0.92 vs. 0.58, all Ps < 0.01). Finally, patients in the chemotherapy group evaluated their actually experienced health states during chemotherapy higher than the chemotherapy scenario that was assessed at the same time (VAS 0.79 vs. 0.69, TTO 0.93 vs. 0.87, SG 0.97 vs. 0.96, all Ps < 0.05). CONCLUSIONS: Both within-group stability and between-group differences were found. A possible explanation for within-group stability may be that the chemotherapy scenario did not fully correspond to the patients' actual experiences with chemotherapy ("noncorresponding description"). Therefore, preferences did not change even when the patients' own clinical health status had changed. The between-group differences may be explained by "anticipated adaptation." Both explanations may work together to explain why utilities remain stable within the same patients but differ between different patient groups.
UI - 11484972
AU - Isambert N; Correia M; Cercueil JP; Zanetta S; Osmak L; Flesch M; Krause
TI - D; Coudert B; Fargeot P; Bedenne L; Chauffert B Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution administered in balloon-occluded hepatic artery: experimental rationale and clinical pilot study.
SO - J Exp Clin Cancer Res 2001 Jun;20(2):183-8
AD - Dept. of Medical Oncology, Regional Anticancer Center Georges-Francois Leclerc, Dijon, France.
Reduced osmolarity in incubation medium was previously shown to increase in vitro cellular accumulation and cytotoxicity of cisplatin on cancer cells. We confirmed in the present work that cisplatin diluted in an hypotonic 25 g/l glucose solution (124 mOsm) was dramatically more cytotoxic in vitro than cisplatin diluted in normotonic 9 g/l NaCl (300 mOsm) on the human HT29 colon and MCF7 breast cancer cells. We conducted then a pilot clinical study on the administration of cisplatin diluted in hypotonic 25 g/l glucose solution given through the balloon-occluded hepatic artery for the treatment of liver metastases from colon or breast cancer tumors. Nine patients (5 men, 4 women; mean age 58, range: 44-71) with confirmed isolated, unresectable metastases from colorectal (7) or breast (2) tumors were included in this study and a total of 23 cycles were administered (2.55 per patient; range 1-5) with an average dose of 50 mg cisplatin (range: 12.5-100). Hepatic artery dissection due to balloon injury with partial or complete arterial obstruction were encountered in 2 patients. Pain in the liver and epigastric area was the main symptom which was constant and intense during the IAH cisplatin injection. Fever > 38 degrees C was observed in 15/23 cycles and increase of creatinine in 1/23 cycles. Transient increase of hepatic transaminases without change in prothrombin time was registered in all patients. However one patient who received the highest dose of 100 mg cisplatin developed a persistent but reversible clinical jaundice and a transient increase in prothrombin time. One patient achieved a partial response (12 weeks), 7 had stable disease (mean duration: 6 weeks) and one had a progressive disease. Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution and administered through the balloon-occluded hepatic artery is a feasible approach. Total dose of cisplatin in hypotonic glucose solution will not exceed 80 mg by cure in a further phase II study.
UI - 11487711
AU - Bell R
TI - Duration of therapy in metastatic breast cancer: management using Herceptin.
SO - Anticancer Drugs 2001 Aug;12(7):561-8
AD - Andrew Love Cancer Centre, 70 Swanston Street, Geelong, Victoria 3220, Australia. email@example.com
Despite progressive developments in therapeutic interventions, including surgery, radiotherapy and chemotherapy, there has been no major improvement in the survival of women with metastatic breast cancer (MBC). Based on knowledge of tumor growth patterns, approaches addressing this issue have included increasing chemotherapy dose or dose density and extending the duration of therapy. However, only the latter approach has resulted in improved clinical benefit, although not survival; and its use is restricted by the cumulative toxicity of chemotherapeutic agents. Therefore, the best hope for improved survival lies with new classes of anticancer drug and particularly biological agents. This review focuses on the first oncogene-targeted therapy for human epidermal growth factor receptor-2 (HER2)+ MBC patients. The humanized anti-HER2 monoclonal antibody