Table of Contents
1
UI - 10856105
AU - Kirkwood JM; Ibrahim JG; Sondak VK; Richards J; Flaherty LE; Ernstoff
TI -
MS; Smith TJ; Rao U; Steele M; Blum RH
High- and low-dose interferon alfa-2b in high-risk melanoma: first
analysis of intergroup trial E1690/S9111/C9190.
SO - J Clin Oncol 2000 Jun;18(12):2444-58
AD - Department of Pathology, University of Pittsburgh Medical Center, PA
15213-2582, USA. jmk@jimmy.harvard.edu
PURPOSE: Pivotal trial E1684 of adjuvant high-dose interferon alfa-2b
(IFNalpha2b) therapy in high-risk melanoma patients demonstrated a
significant relapse-free and overall survival (RFS and OS) benefit
compared with observation (Obs). PATIENTS AND METHODS: A prospective,
randomized, three-arm, intergroup trial evaluated the efficacy of
high-dose IFNalpha2b (HDI) for 1 year and low-dose IFNalpha2b (LDI) for
2 years versus Obs in high-risk (stage IIB and III) melanoma with RFS
and OS end points. RESULTS: A total of 642 patients were enrolled (608
patients eligible), of whom a majority (75%) had nodal metastasis (50%
had nodal recurrence). Unlike E1684, E1690 allowed entry of patients
with T4 (> 4 mm) deep primary tumors, regardless of nodal dissection,
and 25% of the patients entered onto this trial had deep primary tumors
(compared with 11% in E1684). At 52 months' median follow-up, HDI
demonstrated an RFS benefit exceeding that of LDI compared with Obs. The
5-year estimated RFS rates for the HDI, LDI, and Obs arms were 44%, 40%,
and 35%, respectively. The hazards ratio for the intent-to-treat
analysis of HDI versus Obs was 1.28 (P(2) =.05); for LDI versus Obs, it
was 1.19 (P(2) =.17). By Cox analysis, the impact of HDI on RFS achieved
significance (P(2) =.03). The RFS benefit was equivalent for
node-negative and node-positive patients. Neither HDI nor LDI has
demonstrated an OS benefit compared with Obs at this time. A major
improvement in the median OS of patients in the E1690 Obs arm was noted
in comparison with E1684 (6 years v 2.8 years). An analysis of salvage
therapy for patients who relapsed on E1690 demonstrated that a
significantly larger proportion of patients in the Obs arm received
IFNalpha-containing salvage therapy compared with the HDI arm; this
therapy was unavailable to patients during E1684, and patients with
undissected regional nodes were not included in E1684. This study did
not specify therapy at recurrence. Analysis of treatments received at
recurrence demonstrated significantly more frequent use of IFNalpha2b at
relapse from Obs than from HDI, which may have confounded interpretation
of the survival benefit of assigned treatments in E1690. CONCLUSION: The
results of the intergroup E1690 trial demonstrate an RFS benefit of
IFNalpha2b that is dose-dependent and significant for HDI by Cox
multivariable analysis.
2
UI - 11181688
AU - Spitler LE
TI -
Adjuvant therapy of melanoma: at what cost?
SO - J Clin Oncol 2001 Feb 15;19(4):1226-8
3
UI - 11306231
AU - US Preventive Services Task Force
TI -
Screening for skin cancer: recommendations and rationale.
SO - Am J Prev Med 2001 Apr;20(3 Suppl):44-6
4
UI - 11306232
AU - Helfand M; Mahon SM; Eden KB; Frame PS; Orleans CT
TI -
Screening for skin cancer.
SO - Am J Prev Med 2001 Apr;20(3 Suppl):47-58
AD - Division of Medical Informatics and Outcomes Research, Evidence-based
Practice Center, Oregon Health Sciences University, Portland, Oregon
97201-3098, USA. helfand@ohsu.edu
CONTEXT: Malignant melanoma is often lethal, and its incidence in the
United States has increased rapidly over the past 2 decades. Nonmelanoma
skin cancer is seldom lethal, but, if advanced, can cause severe
disfigurement and morbidity. Early detection and treatment of melanoma
might reduce mortality, while early detection and treatment of
nonmelanoma skin cancer might prevent major disfigurement and to a
lesser extent prevent mortality. Current recommendations from
professional societies regarding screening for skin cancer vary.
OBJECTIVE: To examine published data on the effectiveness of routine
screening for skin cancer by a primary care provider, as part of an
assessment for the U.S. Preventive Services Task Force. DATA SOURCES: We
searched the MEDLINE database for papers published between 1994 and June
1999, using search terms for screening, physical examination, morbidity,
and skin neoplasms. For information on accuracy of screening tests, we
used the search terms sensitivity and specificity. We identified the
most important studies from before 1994 from the Guide to Clinical
Preventive Services, second edition, and from high-quality reviews. We
used reference lists and expert recommendations to locate additional
articles. STUDY SELECTION: Two reviewers independently reviewed a subset
of 500 abstracts. Once consistency was established, the remainder were
reviewed by one reviewer. We included studies if they contained data on
yield of screening, screening tests, risk factors, risk assessment,
effectiveness of early detection, or cost effectiveness. DATA
EXTRACTION: We abstracted the following descriptive information from
full-text published studies of screening and recorded it in an
electronic database: type of screening study, study design, setting,
population, patient recruitment, screening test description, examiner,
advertising targeted at high-risk groups or not targeted, reported risk
factors of participants, and procedure for referrals. We also abstracted
the yield of screening data including probabilities and numbers of
referrals, types of suspected skin cancers, biopsies, confirmed skin
cancers, and stages and thickness of skin cancers. For studies that
reported test performance, we recorded the definition of a suspicious
lesion, the "gold-standard" determination of disease, and the number of
true positive, false positive, true negative, and false negative test
results. When possible, positive predictive values, likelihood ratios,
sensitivity, and specificity were recorded. DATA SYNTHESIS: No
randomized or case-control studies have been done that demonstrate that
routine screening for melanoma by primary care providers reduces
morbidity or mortality. Basal cell carcinoma and squamous cell carcinoma
are very common, but detection and treatment in the absence of formal
screening are almost always curative. No controlled studies have shown
that formal screening programs will improve this already high cure rate.
While the efficacy of screening has not been established, the screening
procedures themselves are noninvasive, and the follow-up test, skin
biopsy, has low morbidity. Five studies from mass screening programs
reported the accuracy of skin examination as a screening test. One of
these, a prospective study, tracked patients with negative results to
determine the number of patients with false-negative results. In this
study, the sensitivity of screening for skin cancer was 94% and
specificity was 98%. Several recent case-control studies confirm earlier
evidence that risk of melanoma rises with the presence of atypical moles
and/or many common moles. One well-done prospective study demonstrated
that risk assessment by limited physical exam identified a relatively
small (<10%) group of primary care patients for more thorough
evaluation. CONCLUSIONS: The quality of the evidence addressing the
accuracy of routine screening by primary care providers for early
detection of melanoma or nonmelanoma skin cancer ranged from poor to
fair. We found no studies that assessed the effectiveness of periodic
skin examination by a clinician in reducing melanoma mortality. Both
self-assessment of risk factors or clinician examination can classify a
small proportion of patients as at highest risk for melanoma. Skin
cancer screening, perhaps using a risk-assessment technique to identify
high-risk patients who are seeing a physician for other reasons, merits
additional study as a strategy to address the excess burden of disease
in older adults.
5
UI - 11417749
AU - Dreau D; Foster M; Hogg M; Swiggett J; Holder WD; White RL
TI -
Angiogenic and immune parameters during recombinant interferon-alpha2b
adjuvant treatment in patients with melanoma.
SO - Oncol Res 2001;12(5):241-51
AD - Department of General Surgery Research, Carolinas Medical Center,
Charlotte, NC 28203, USA. ddreau@carolinas.org
As an adjuvant therapy for patients with high risk of recurrent
melanoma, high-dose interferon (IFN)-alpha2b therapy has been shown to
have some efficacy. We examined 22 patients with resected melanoma who
were treated with repeated injections of recombinant IFN-alpha2b during
the treatment. Both angiogenic and immune parameters were measured.
White blood cells (WBCs) and lymphocyte numbers, lymphocyte
subpopulations, serum concentrations of IFN-alpha and anti-IFN-alpha
antibodies, and the serum vascular endothelial growth factor (VEGF),
interleukin (IL)-8, and basis fibroblast growth factor (bFGF)
concentrations were determined over time in resected, recurrence-free
patients with American Joint Committee on Cancer (AJCC) stage III
melanoma with one or less (LN+ < or = 1, n = 7) or more than one (LN+ >
1, n = 8) lymph nodes involved, and AJCC stage IV resected disease (n =
7). Follow-up and recurrence-free intervals were longer in stage III
(LN+ < or = 1) patients compared with stage IV patients (P < 0.05). The
number of WBCs and lymphocytes decreased during the treatment for all
patient groups (P < 0.001). In addition, percentages of CD8 and CD20
were higher in stage IV patients than in stage III (LN+ > 1) and stage
III (LN+ < or = 1) patients at the beginning of therapy (P < 0.05). A
significant increase in the percentage of CD20+ cells, mostly B
lymphocytes, was observed in the stage III (LN+ > 1) and stage III (LN+
< or = 1) patients over time but not in stage IV patients (P < 0.001).
Low IL-8 and bFGF concentrations at the beginning of therapy were
associated with significantly longer recurrence-free survival (P <
0.05). These results warrant a larger trial to determine if the
differences observed in patients before treatment can provide prognostic
markers in patients receiving IFN-alpha2b therapy.
6
UI - 11440180
AU - Drzewiecka A; Urbanska K; Matuszak Z; Pineiro M; Arnaut LG; Habdas J;
TI -
Ratuszna A; Stochel G
Tritolylporphyrin dimer as a new potent hydrophobic sensitizer for
photodynamic therapy of melanoma.
SO - Acta Biochim Pol 2001;48(1):277-82
AD - Faculty of Chemistry, Jagiellonian University, Krakow, Poland.
We report the synthesis, photochemical and photophysical properties and
preliminary studies on biological effect of a new tritolylporphyrin
dimer (T-D). Absorption and emission properties of T-D suggest its
possible use in photodynamic therapy. T-D is capable of singlet oxygen
production with 0.8 quantum yield. It also has a high photostability.
The photodynamic properties of the dimer were examined following the
growth of SKMEL 188 (human melanoma) cells irradiated with red light
(cut off < 630 nm). The surviving fraction of the cells decreased about
3-fold (vs. non-irradiated cells) for an 81 J/cm dose. Our results
suggest that tritolylporphyrine dimer T-D may be an interesting
hydrophobic sensitizer for photodynamic therapy.
7
UI - 11418308
AU - Dillman RO; DeLeon C; Beutel LD; Barth NM; Schwartzberg LS; Spitler LE;
TI -
Garfield DH; O'Connor AA; Nayak SK
Short-term autologous tumor cell lines for the active specific
immunotherapy of patients with metastatic melanoma.
SO - Crit Rev Oncol Hematol 2001 Jul-Aug;39(1-2):115-23
AD - Hoag Cancer Center, One Hoag Drive, Building 41, Newport Beach, CA
92658, USA. rdillman@hoaghospital.org
We established short-term cell lines for 108/170 (64%) patients with
metastatic melanoma. Tumor cell numbers were expanded to 10(8), then
cells were irradiated, aliquoted, and cryopreserved for clinical use.
Vaccines have been used to treat 69 patients with clinical follow up for
33 who had measurable metastatic disease at the time vaccine therapy was
initiated (METS), and 33 who had no evidence of disease (NED) at the
time of vaccine therapy following surgical resection of metastases. The
protocol called for a baseline test of delayed tumor hypersensitivity
(DTH), three weekly injections, a repeat of the DTH test, then monthly
injections for an additional 5 months. Objective tumor responses were
noted in 3/26 (12%) patients who received a minimum of three
vaccinations, one complete, and two partial, with survivals of 36, 46+,
and 78+ months. Only 6/64 (9.4%) had a positive DTH (>10 mm) at
baseline, including three METS, all of whom progressed within 4 months
and died within a year, and three who are still NED after more than 5
years. Conversion of DTH from negative to positive was documented in
18/44 (41%) patients who were tested at week 0 and 4. At a median follow
up of greater than 5 years, the median overall survival (OS) was 40
months for "NED" with a 5-year survival rate of 39%, and 8.6 months with
a 5-year survival rate of 10% for "METS" The 18 patients who had
conversion of their DTH had a median event-free survival (EFS) of 15.8
months and 5-year EFS of 32% compared to 4.2 months and 9% for the 26
non-converters (P=0.012, two-tailed, log-rank test). Among patients who
were NED when treatment started, the 12 patients whose DTH converted had
a median overall survival of 61.4 months with 5-year survival of 63%
compared to 9.7 months and 0% for the 13 non-converters (P=0.0026). This
treatment approach is feasible, produces minimal toxicity, and is
associated with long-term survival in a significant subset of patients.
8
UI - 11485637
AU - Kaufman HL; DeRaffele G; Divito J; Horig H; Lee D; Panicali D; Voulo M
TI -
A phase I trial of intralesional rV-Tricom vaccine in the treatment of
malignant melanoma.
SO - Hum Gene Ther 2001 Jul 20;12(11):1459-80
AD - Abert Einstein Cancer Center, Bronx, New York 10461, USA.
kaufman@aecom.yu.edu
9
UI - 11504282
AU - Sondak VK
TI -
Adjuvant therapy for melanoma.
SO - Cancer J 2001 Jul-Aug;7 Suppl 1():S24-7
AD - Division of Surgical Oncology, University of Michigan Medical School,
Ann Arbor, USA.
Patients with deep primaries (> or = 4 mm) or regional lymph node
involvement often require adjuvant therapy in addition to surgery to
successfully treat melanoma. Various adjuvant strategies are reviewed.
Randomized trials of IFN-alpha adjuvant therapy have demonstrated
statistically significant improvements in disease-free and overall
survival rates, leading to approval by the United States Food and Drug
Administration of the use of 1 year of intensive IFN-alpha2b following
surgical resection of high-risk disease. A study comparing high-dose IFN
with the ganglioside vaccine GMK was terminated early when the Data
Safety Monitoring Committee concluded that the high-dose IFN treatment
arm was associated with highly significantly improved relapse-free and
overall survival. Studies of IFN-alpha in stage I and II melanoma are
reviewed. Dose and schedule issues in the use of IFN-alpha are
addressed. In addition to adjuvant therapy with IFN-alpha, various other
treatment strategies appear promising. Adjuvant vaccine therapy may be
useful for treatment of cutaneous melanoma. Polyvalent melanoma vaccines
are discussed as a potential adjuvant therapy. Finally, nonrandomized
preliminary studies suggest that postoperative radiation to the neck or
axilla after radical lymph node dissection may decrease regional
recurrence rates in node-positive patients, supporting the selective use
of radiation therapy for melanoma.
10
UI - 11555334
AU - Weinstock MA
TI -
Sunscreen use can reduce melanoma risk.
SO - Photodermatol Photoimmunol Photomed 2001 Oct;17(5):234-36; discussion
236-7
AD - Dermatoepidemiology Unit, V.A. Medical Center 11-D, 830 Chalkstone
Avenue, Providence, RI 02908, USA. maw@brown.edu
11
UI - 11564919
AU - Mercier GA; Alavi A; Fraker DL
TI -
FDG positron emission tomography in isolated limb perfusion therapy in
patients with locally advanced melanoma: preliminary results.
SO - Clin Nucl Med 2001 Oct;26(10):832-6
AD - Division of Nuclear Medicine, Department of Radiology, University of
Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
PURPOSE: Isolated limb perfusion (ILP) with high-dose chemotherapy and
tumor necrosis factor is being tested in clinical trials as a treatment
for locally advanced extremity melanoma. The authors investigated the
ability of F-18 fluorodeoxyglucose positron emission tomography (FDG
PET) to determine the true extent of disease in patients with this
condition, whose distribution of lesions differs from that seen in
previous studies. METHODS: Nine patients with locally advanced melanoma
were selected for imaging of the entire body and extremities using FDG
PET from a group of participants in a clinical trial of ILP with
melphalan +/- tumor necrosis factor. Scans were obtained without
attenuation correction. Post-treatment scans were obtained in three
patients 1 month after ILP. The findings in the FDG-PET scans were
compared with those of a standard protocol (SP) that included anatomic
images and physical examinations. RESULTS: Eighty lesions (74 malignant,
6 benign) were detected with FDG PET and the SP combined. Only malignant
lesions were detected by both methods in the perfused limbs. Of the
malignant lesions, FDG PET detected 65 lesions (sensitivity rate, 88%).
In contrast, 48 lesions were detected with the SP (sensitivity rate,
65%). Twenty-six malignant lesions were seen only with FDG PET (35%),
whereas nine malignant lesions were seen only with SP (12%). The six
benign lesions included three false-positive mediastinal lymph nodes in
one patient. The accuracy rates of FDG PET and the SP were 83% and 65%,
respectively. These results are comparable to those seen in previous
studies with patients who had disease confined primarily to the torso.
All post-therapy FDG-PET scans showed a reduction in the number of
visualized limb lesions, and diffuse uptake throughout the perfused
limbs. The diffuse uptake correlated with post-therapy limb
inflammation. CONCLUSIONS: Non-attenuation-corrected FDG PET is more
sensitive than the SP in detecting the extent of disease in candidates
for ILP. The FDG uptake associated with post-therapy inflammation may
reduce the contrast resolution of this technique and must be evaluated
further.
12
UI - 11596037
AU - Joukhadar C; Klein N; Mader RM; Schrolnberger C; Rizovski B; Heere-Ress
TI -
E; Pehamberger H; Strauchmann N; Jansen B; Muller M
Penetration of dacarbazine and its active metabolite
5-aminoimidazole-4-carboxamide into cutaneous metastases of human
malignant melanoma.
SO - Cancer 2001 Oct 15;92(8):2190-6
AD - Department of Clinical Pharmacology, Division of Clinical
Pharmacokinetics, University of Vienna Medical School, Vienna, Austria.
BACKGROUND: Dacarbazine has been on the market for approximately 3
decades but remains the most effective single agent available for the
therapy of metastatic malignant melanoma (MMM). Most MMMs, however,
respond poorly to dacarbazine therapy. Apart from tumor resistance at a
molecular level, several studies support the notion that therapeutic
failure in tumor therapy also might be attributed to an impaired
transcapillary drug transfer. METHODS: On the basis of this hypothesis,
the authors measured intratumor transcapillary transfer rates of
dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide
(AIC) by in vivo microdialysis after intravenous administration of
dacarbazine at doses of 200 mg/m(2) to 1000 mg/m(2) (n = 7) in patients
suffering from MMM. RESULTS: For all doses, area under the concentration
curve (AUC) values for dacarbazine and AIC were not significantly
different between plasma and tumor interstitium with
AUC(tumor)/AUC(plasma) ratios of 0.97 +/- 0.08 (mean +/- standard error
of the mean) for dacarbazine and 0.76 +/- 0.22 for AIC. AUC(0-240)
values for dacarbazine and AIC measured in plasma correlated closely
with corresponding AUC(0-240)values measured in the interstitium of MMMs
with values of r(s) = 0.82 (P = 0.042) and r(s) = 0.90 (P = 0.037),
respectively. CONCLUSIONS: The results of this study indicate favorable
tumor penetration characteristics of dacarbazine and its active
metabolite AIC. The relative lack of response to antineoplastic therapy
with dacarbazine, thus might be explained by resistance of melanoma
cells at a molecular level rather than by an inability of dacarbazine
and AIC to penetrate into the interstitium of MMM. Copyright 2001
American Cancer Society.
13
UI - 11595689
AU - Slingluff CL Jr; Yamshchikov G; Neese P; Galavotti H; Eastham S;
TI -
Engelhard VH; Kittlesen D; Deacon D; Hibbitts S; Grosh WW; Petroni G;
Cohen R; Wiernasz C; Patterson JW; Conway BP; Ross WG
Phase I trial of a melanoma vaccine with gp100(280-288) peptide and
tetanus helper peptide in adjuvant: immunologic and clinical outcomes.
SO - Clin Cancer Res 2001 Oct;7(10):3012-24
AD - Department of Surgery, University of Virginia, Charlottesville, 22908,
USA. cls8h@virginia.edu
A melanoma vaccine composed of HLA-A2-restricted peptide YLEPGPVTA
(gp100(280)), with or without a modified T-helper epitope from tetanus
toxoid AQYIKANSKFIGITEL, has been evaluated in a Phase I trial to assess
safety and immunological response. The vaccines were administered s.c.
in either of two adjuvants, Montanide ISA-51 or QS-21, to 22 patients
with high-risk resected melanoma (stage IIB-IV). Local and systemic
toxicities were mild and transient. We detected CTL responses to the
gp100(280) peptide in peripheral blood in 14% of patients. Helper T-cell
responses to the tetanus helper peptide were detected in 79% of patients
and had a Th1 cytokine profile. One patient with a CTL response to gp100
had a recurrence in a lymph node 2 years later; her nodes contained CD8+
cells reactive to gp100(280) (0.24%), which proliferated in response to
peptide. The overall survival of patients is 75% (95% confidence
interval, 57-94%) at 4.7 years follow-up, which compares favorably with
expected survival. Four of 14 patients who completed at least six
vaccines subsequently developed metastases, all of which were solitary
and surgically resectable. They remain alive and clinically free of
disease at last follow-up. Data from this trial demonstrate
immunogenicity of the gp100(280) peptide and suggest that immune
responses may persist long-term in some patients. The frequency and
magnitude of the CTL response may be improved with more aggressive
vaccination regimens. Although this Phase I study was not intended to
evaluate clinical benefit, the excellent survival of patients on this
protocol suggests the possibility of a benefit that should be assessed
in future studies.
14
UI - 11605226
AU - Ryuto M; Higaki Y; Tomita K
TI -
[Clinical analysis of 16 cases of malignant head and neck melanoma]
SO - Nippon Jibiinkoka Gakkai Kaiho 2001 Sep;104(9):859-65
AD - Division of Head and Neck, National Kyushu Cancer Center, Fukuoka.
Subjects were 16 patients--5 men and 11 women aged 46-82 years (mean: 61
years)--with malignant melanoma of the head and neck treated at our
clinic from 1972 to 1988. Histologically, 1 subjects was amelanotic and
15 melanotic type. Primary lesions were 10 involving the nasal cavity, 2
the paranasal sinus, 2 the gingiva, 1 the lip, and 1 primary unknown.
They were treated with or without multimodal surgery, radiation,
chemotherapy, and immunotherapy. Of 12 treated using local surgery,
local recurrence was seen in 6 in 7 areas. Two-year survival was 44% and
5-year survival 22%. The prognosis of malignant head and neck melanoma
is poor but has gradually improved due to preoperative decisions on
disease spread and the introduction of multimodal therapy.
15
UI - 11603540
AU - Payne WG; Kearney R; Wells K; Blue M; Walusimbi M; Mosiello G; Cruse CW;
TI -
Reintgen D
Desmoplastic melanoma.
SO - Am Surg 2001 Oct;67(10):1004-6
AD - Department of Surgery, University of South Florida, Tampa, USA.
Desmoplastic melanoma is an uncommonly encountered variant of malignant
melanoma. Three histological subtypes exist: desmoplastic, neurotropic,
and neural transforming. Desmoplastic melanoma commonly presents in
conjunction with existing melanocytic lesions or as an amelanotic firm
nodule. Local recurrences are common. Thirty patients over a 6-year
period were treated at our institution for desmoplastic melanoma. All
lesions were treated with local excision. Local recurrence occurred in
seven patients (23%) and was treated by aggressive re-excision in each
instance. Clinical regional metastasis (lymph nodal basins) were
detected in two patients (6%). Distant metastasis (lung) developed in
two patients (6%). Twenty-three patients (76%) were found to have
desmoplastic subtype, whereas five (17%) had neurotropic subtype. Six
patients (20%) had associated pigmented melanotic lesions. Average
length of follow-up has been 18 months. Overall survival is 96 per cent.
Presentations and histologic diagnosis can sometimes be difficult and
misleading. Treatment is aggressive local excision with follow-up
necessary to detect resectable recurrent lesions.
16
UI - 11641093
AU - Lejeune FJ; Kroon BB; Di Filippo F; Hoekstra HJ; Santinami M; Lienard D;
TI -
Eggermont AM
Isolated limb perfusion: the European experience.
SO - Surg Oncol Clin N Am 2001 Oct;10(4):821-32, ix
AD - Multidisciplinary Oncology Center, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland. ferdy.lejeune@chuv.hospvd.ch
Isolated limb perfusion (ILP) is a method of cancer treatment allowing
the administration of high doses of anticancer agents in a limb
surgically isolated from systemic circulation. By using continuous
leakage monitoring and using the drug melphalan, a high complete
remission rate is obtained in patients with melanoma. In patients with
sarcomas, ILP with tumor necrosis factor and melphalan represents a
neoadjuvant treatment for limb-sparing surgery. This treatment is the
first demonstration of an active anti-angiogenic regimen in the clinic.
17
UI - 11641099
AU - Santinami M; Maurichi A; Patuzzo R; Pennacchioli E; Cascinelli N
TI -
Impact of clinical trials on the treatment of melanoma.
SO - Surg Oncol Clin N Am 2001 Oct;10(4):935-47, xi
AD - Department of Surgery, Instituto Nazionale per lo Studio e la Cura dei
Tumori, Milan, Italy.
Today the role of clinical trials is being challenged and it seems that
this investigative tool does not keep in step with the rhythms imposed
by the progress of scientific knowledge and the expectations of the
public and media. From the 1970's to the 1990's, however, clinical
trials have been the most important way for clinical researchers to find
answers to therapeutic questions.
18
UI - 11675517
AU - Gershenwald JE
TI -
Melanoma.
SO - Oncologist 2001;6(5):402-6
AD - The University of Texas M.D. Anderson Cancer Center, Houston, Texas
77030, USA. jgershen@mdanderson.org
The presentations at the American Society of Clinical Oncology 2001
meeting reported or updated the results of phase I, II, and III
randomized trials and also reported important meta-analyses and
retrospective studies impacting on the management of patients with
melanoma. In the treatment of early stage melanoma, the prognostic
significance of pathologic status of sentinel lymph nodes was affirmed.
With respect to regional nodal involvement (American Joint Committee on
Cancer [AJCC] stage III), investigators presented the interim results of
the United Kingdom randomized low-dose interferon (IFN) trial, and
up-to-date meta-analyses of several IFN trials including a pooled
analysis of the Eastern Cooperative Oncology Group trials evaluating
interferon in the adjuvant setting. In the advanced disease setting
(AJCC stage IV), several studies elucidated the pros and cons of
biochemotherapy in patients with metastatic melanoma, with an emphasis
on seeking to improve response in the central nervous system and
durability of response in general. Thought provoking was new data
regarding the potential for lovastatin to act as a chemopreventive agent
for melanoma. Translational studies were presented, one supporting the
importance of HLA-typing in developing targeted vaccine therapy.
Finally, the results of a novel experimental melanoma vaccine were
presented using autologous tumor-derived heat-shock protein peptide
complex-96 (HSPPC-96).
19
UI - 11677100
AU - Eggermont AM
TI -
The role interferon-alpha in malignant melanoma remains to be defined.
SO - Eur J Cancer 2001 Nov;37(17):2147-53
AD - Department of Surgical Oncology, Erasmus University Medical
Center--Daniel den Hoed Cancer Center, 301 Groene Hilledijk, 3075 EA
Rotterdam, The Netherlands. eggermont@chih.azr.nl
Interferon-alpha (IFNalpha) is a pleiotropic cytokine with various
direct and indirect inflammatory response modulating activities. Some of
these activities may have direct or indirect antitumour effects. For
such a wide range of biological activities, the dose for optimal
biological activity may differ greatly from the maximally tolerated dose
as different effects are mediated by different concentrations of
IFNalpha. Because of its immunomodulatory effects, it has been
extensively studied in melanoma patients. Little antitumour activity has
been demonstrated in metastatic stage IV melanoma, with overall response
rates of 10-15%, which were not dose-related. Yet, IFNalpha has been
widely studied in the adjuvant setting for stage II and III disease.
Many trials have been underpowered, have used very heterogeneously mixed
patient populations, a wide variety of doses and treatment schedules,
and have suffered from early and unplanned analyses. Mature data are
still pending in some 3000 patients of the overall approximately 6000
patients that participated in the adjuvant trials. A meta-analysis has
demonstrated a similar impact on relapse-free survival across various
dose ranges of IFNalpha, but no significant impact on overall survival
(OS). In light of the lack of impact on OS and the considerable to
serious dose-dependent toxicity of IFNalpha, we do not have a clearly
dose- and schedule-defined role for IFNalpha in the adjuvant setting and
have no evidence for a benefit of IFNalpha in stage IV melanoma. For the
adjuvant setting, the main question: efficacy of very toxic high dose
therapy versus efficacy of non-toxic long-term treatment will be
answered by the mature data from the large US-Intergroup high-dose and
EORTC intermediate-dose and long-term maintenance therapy trials.
20
UI - 11688150
AU - Kampgen E; Becker J; Brocker EB
TI -
[Cell therapy with dendritic cells]
SO - Internist (Berl) 2001 Oct;42(10):1314-20
AD - Universitat Wurzburg, Klinik und Poliklinik fur Haut- und
Geschlechtskrankheiten, Josef-Schneider-Strasse 2, 97080 Wurzburg.
Kaempgen-e.derma@mail.uni-wuerzburg.de
21
UI - 11693798
AU - Bajetta E; Del Vecchio M; Vitali M; Martinetti A; Ferrari L; Queirolo P;
TI -
Sertoli MR; Cainelli T; Cellerino R; Cascinelli N
A feasibility study using polychemotherapy (cisplatin + vindesine +
dacarbazine) plus interferon-alpha or monochemotherapy with dacarbazine
plus interferon-alpha in metastatic melanoma.
SO - Tumori 2001 Jul-Aug;87(4):219-22
AD - Unit of Medical Oncology B, Istituto Nazionale per lo Studio e la Cura
dei Tumori, Milan, Italy. bajetta@istitutotumori.mi.it
AIMS AND BACKGROUND: This trial evaluated the feasibility and
tolerability of an immunochemotherapeutic approach that uses cisplatin,
vindesine, and dacarbazine (DTIC), or only DTIC, in combination with
interferon alpha-2a (IFN-alpha), in patients with metastatic melanoma,
considering the significant toxicity of several different regimens used
patients (50 of whom were assessable) entered a multicentric trial and
were randomized to receive cisplatin (30 mg/m2 daily for 3 days) +
vindesine (2.5 mg/m2 only day 1) + DTIC (250 mg/m2 daily for 3
consecutive days) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (CVD arm)
versus DTIC (800 mg/m2 day 1) + IFN-alpha (3 MIU i.m. 3x/wk
continuously) (DTIC arm). The chemotherapy was recycled every 21 days.
Patient reevaluation was performed every two cycles, and the treatment
was continued in case of objective response or stabilization of disease.
RESULTS: We observed 3 complete responses, 2 partial responses and 5
stable diseases in the CVD arm, and 2 partial responses and 4
stabilizations of disease in the DTIC arm. CONCLUSIONS: We conclude that
these chemotherapeutic regimens are well tolerated regimens with modest
toxicity. Future trials will be conducted associating the CVD regimen
with biological response modifiers (IFN, IL-2) in order to improve the
results.
22
UI - 11693825
AU - Morton DL
TI -
Cytoreductive surgery and adjuvant immunotherapy in the management of
metastatic melanoma.
SO - Tumori 2001 Jul-Aug;87(4):S57-9
AD - Roy E Coats Research Laboratories, John Wayne Cancer Institute at Saint
John's Health Center, Santa Monica, CA 90404, USA. mortond@jwci.org
23
UI - 11693827
AU - Eggermont AM
TI -
Frontiers in adjuvant therapy in stage II-III melanoma.
SO - Tumori 2001 Jul-Aug;87(4):S60-3
AD - Department of Surgical Oncology. University Hospital Rotterdam, Daniel
Den Hoed Cancer Center Rotterdam, The Netherlands. eggermont@chih.azr.nl
24
UI - 11698460
AU - Blanchet JS; Valmori D; Dufau I; Ayyoub M; Nguyen C; Guillaume P;
TI -
Monsarrat B; Cerottini JC; Romero P; Gairin JE
A new generation of Melan-A/MART-1 peptides that fulfill both increased
immunogenicity and high resistance to biodegradation: implication for
molecular anti-melanoma immunotherapy.
SO - J Immunol 2001 Nov 15;167(10):5852-61
AD - Laboratoire d'ImmunoPharmacologie Structurale, Institut de Pharmacologie
et Biologie Structurale, Centre National de la Recherche Scientifique,
Toulouse, France.
Intense efforts of research are made for developing antitumor vaccines
that stimulate T cell-mediated immunity. Tumor cells specifically
express at their surfaces antigenic peptides presented by MHC class I
and recognized by CTL. Tumor antigenic peptides hold promise for the
development of novel cancer immunotherapies. However, peptide-based
vaccines face two major limitations: the weak immunogenicity of tumor
Ags and their low metabolic stability in biological fluids. These two
hurdles, for which separate solutions exist, must, however, be solved
simultaneously for developing improved vaccines. Unfortunately, attempts
made to combine increased immunogenicity and stability of tumor Ags have
failed until now. Here we report the successful design of synthetic
derivatives of the human tumor Ag Melan-A/MART-1 that combine for the
first time both higher immunogenicity and high peptidase resistance. A
series of 36 nonnatural peptide derivatives was rationally designed on
the basis of knowledge of the mechanism of degradation of Melan-A
peptides in human serum and synthesized. Eight of them were efficiently
protected against proteolysis and retained the antigenic properties of
the parental peptide. Three of the eight analogs were twice as potent as
the parental peptide in stimulating in vitro Melan-specific CTL
responses in PBMC from normal donors. We isolated these CTL by
tetramer-guided cell sorting and expanded them in vitro. The resulting
CTL efficiently lysed tumor cells expressing Melan-A Ag. These
Melan-A/MART-1 Ag derivatives should be considered as a new generation
of potential immunogens in the development of molecular anti-melanoma
vaccines.
25
UI - 11710284
AU - Akimov MA; Gershanovich ML
TI -
[Clinical evaluation of the efficacy of modern first, second, and third
line regimes of chemotherapy in patients with disseminated cutaneous
melanoma]
SO - Vopr Onkol 2001;47(4):428-35
AD - N.N. Petrov Research Institute of Oncology, Ministry of Health of the
RF, St. Petersburg.
The effectiveness and side-effects of various chemotherapy (CT) regimens
were compared in 157 patients (74 males and 80 females, aged 23-79) with
disseminated skin melanoma (DSM). Most cases had multiple metastases to
the skin and subcutaneous fat tissue, regional lymph nodes (59-69%),
lung (14-38%) and liver (13-36%); to other sites--82 (52%). Total
response in the dacarbazine (DTIC) group was 18% (complete--5,
partial--13 and stabilization--29%). DTIC was employed as first-line
treatment in 71%. DBDT (cisplatin, DTIC, BCNU, tamoxifen) was used in 42
patients: as first-line--13 (31%), second-line--21 (50%) and third-line
(following the first two regimens in cases refractory to treatment or
those with response-based evidence of tumor progression)--8 (19%). In
DBDT-treated patients, total response was 29% (complete--7, partial 22
and stabilization--38%). Similar results were recorded in the group
where 69% were given CT as second- and third-line treatment. The effect
of CVD (cisplatin, vinblastin, DTIC) was much the same as that of DTIC
alone but was followed by a higher incidence of myelodepression and
anemia. Combined treatment with prospidin+ CCNU + BCNU seems to offer
more advantage.
26
UI - 11715595
AU - Claassen AT; van Berlo CL; Coebergh JW
TI -
[Melanoma of the skin: excision policy and pathology report writing in
the 'Integraal Kankercentrum Zuid' region is in accordance with the
guideline in slightly more than half of the patients]
SO - Ned Tijdschr Geneeskd 2001 Oct 27;145(43):2079-83
AD - St. Maartens Gasthuis, afd. Chirurgie, Venlo. acla@surgery.azm.nl
OBJECTIVE: To determine the extent to which the guidelines for cutaneous
melanoma had been implemented in the diagnostic and treatment approach
of general hospitals. DESIGN: Retrospective, descriptive. METHOD:
Patients were selected via the cancer registration system of the
'Integraal Kankercentrum Zuid' (Integral Cancer Centre South, the
Netherlands). They were submitted through the pathology laboratory by 1
of the 16 general hospitals in the region. Data was collected from the
pathology (PA) reports of the 573 patients for whom a cutaneous melanoma
was diagnosed in 1988, 1993 and 1997. The treatment policy and the PA
reports were compared with the recommendations in the guidelines
concerned and the revised versions of these published in 1985, 1990 and
1997. The patients studied were 212 men (37%) and 361 women (63%) with
an average age of 51 years (range 13-96). RESULTS: A diagnostic excision
was performed in 485/573 patients (85%). Invasiveness was assessed in
99% of the preparations; in 14% a melanoma was encountered in situ.
Invasive melanomas were less often seen in the head and neck region than
on the trunk or limb. Thickness of the tumour was not determined in 8%
of all 493 invasive tumours and in 19% the pathology report did not
state whether the diagnostic biopsy was performed radically. In
accordance with the guidelines, diagnostic excision biopsy was first
performed in 59% of patients with a subsequent re-excision if necessary;
77% of the PA reports satisfied the fundamental recommendations from the
guidelines. For 55% of the patients the diagnostic and therapeutic
procedures as well as the pathology report were completed in accordance
with the guideline recommendations. Modest improvement occurred over
time. CONCLUSION: The excision and re-excision policies as well as the
pathology report writing concurred with the recommendations in the
consensus for cutaneous melanoma in slightly more than half of the
patients who were diagnosed within the IKZ region in the years 1988,
1993 and 1997.
27
UI - 11712820
AU - Nieboer P; Mulder NH; Van Der Graaf WT; Willemse PH; Hospers GA
TI -
Dacarbazine DTIC and carboplatin as an outpatient treatment for
disseminated malignant melanoma.
SO - Anticancer Res 2001 Jul-Aug;21(4B):3115-6
AD - Department of Medical Oncology, University Hospital Groningen, The
Netherlands.
Occasionally long-term survival in disseminated melanoma can be obtained
through chemotherapy. We treated 22 patients with disseminated melanoma
with an outpatient regimen consisting of dacarbazine (DTIC) and
carboplatin. Three patients had a complete response lasting 4+, 9 and 9
months (survival 4+, 10 and 16 months), respectively; 3 patients had a
partial response lasting 4, 6 and 8 months (survival 6+, 11+ and 14
months), respectively. Overall response was 27% (95% confidence interval
11-50%). Toxicity was relatively mild and mainly due to nausea. In 3
patients the dose of carboplatin was reduced because of grade 4
haematological toxicity. This described easy outpatient regimen shows
comparable results as other polychemotherapeutic regimens in
disseminated melanoma, but with a relatively mild toxicity profile.
28
UI - 11727535
AU - Wang E; Phan GQ; Marincola FM
TI -
T-cell-directed cancer vaccines: the melanoma model.
SO - Expert Opin Biol Ther 2001 Mar;1(2):277-90
AD - Surgery Branch, National Cancer Institute, National Institutes of
Health, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892,
USA.
Significant advances in the understanding of the molecular basis for
tumour/host interactions in humans have occurred in the last decade
through studying patients with metastatic melanoma. This disease is
characterised by its tendency to be modulated by immunologic factors.
Furthermore, immunologic manipulation of the host with various systemic
agents, in particular IL-2, frequently affects this natural phenomenon
and can lead to complete rejection of cancer. By studying the cellular
immunology occurring in patients undergoing immunotherapy, several
tumour antigens (TA) and their epitopes recognised by human leukocyte
antigen (HLA) class I-restricted cytotoxic T-lymphocytes (CTL) have been
identified. Most of these TA are non-mutated molecules expressed by the
majority of melanoma in vivo and most melanoma cell lines. In addition,
unique minimal epitopic sequences play an immunodominant role in the
context of specific HLA class I alleles. Since melanoma lesions from
different patients often share expression of the same TA, and a minimal
peptide sequence from a TA can cause immunologic changes in multiple
patients, interest has grown in the development of TA-specific vaccines
suitable for broad patient populations. Repeated in vitro stimulation of
peripheral blood mononuclear cells (PBMC) with TA-derived epitopes can
induce a high frequency of TA-reactive T-cells in melanoma patients. The
same epitopes can also enhance TA-specific T-cell reactivity in vivo
when administered subcutaneously in combination with Incomplete Freund's
Adjuvant (IFA). Epitope-based vaccinations, however, have not shown
strong clinical efficacy unless combined with IL-2 administration.
Attempts to increase the efficacy of these vaccines have combined
specialised antigen-presenting cells or the administration of whole TA
through DNA- or RNA-based vaccines with the intention of increasing
antigen presentation and processing. Save for scattered reports,
however, the success of these approaches has been limited and
T-cell-directed vaccination against cancer remains at a paradoxical
standstill whereby anticancer immunisation can be induced but it is not
sufficient, in most cases, to induce tumour regression. Using melanoma
as the standard model for immunotherapy, we will review various methods
of T-cell-directed vaccination, the monitoring and analysis of the
resulting immune response, and several clinical trials in which cancer
vaccines have successfully induced immunisation.
29
UI - 11727521
AU - Marchand M; Brichard V; van Baren N; Coulie PG
TI -
Biological and clinical developments in melanoma vaccines.
SO - Expert Opin Biol Ther 2001 May;1(3):497-510
AD - Ludwig Institute for Cancer Research, Brussels Branch, Avenue Hippocrate
74, BP 7459, B-1200 Brussels, Belgium. marie.marchand@bru.licr.org
The identification of antigens recognised on human tumours by autologous
T-lymphocytes has opened the way for vaccination strategies involving
defined tumour antigens. These vaccinations are therapeutic, i.e. they
involve patients with detectable disease. Tumour regressions have been
observed in a minority of melanoma patients in Phase I/II trials. Some
of these regressions have been complete and long lasting. Improving the
efficacy of therapeutic vaccines will critically depend on their
capacity to trigger a robust immune response, on the development of
appropriate methods to monitor these antitumour immune responses to
vaccination and on a better understanding of the mechanisms used by
tumours to escape immune attack. Finally, the initiation of large
randomised Phase III trials will determine the impact of these vaccines
on melanoma treatment.
30
UI - 11718143
AU - Anonymous
TI -
Special report: vaccines for the treatment of malignant melanoma.
SO - Tecnologica MAP Suppl 2001 Apr 13;():19-20
This Special Report is a summary of the background for an evidence-based
analysis of the phase I/II clinical trial data supporting currently open
or recently closed phase III trials of melanoma vaccine therapy. It does
not attempt to address the question as to whether the TEC criteria are
met. Note, however, that since no melanoma vaccine as yet has FDA
About OncoLink Contact OncoLink Privacy statement Disclaimer Link to OncoLink Home