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NCI CANCERLIT® Search: Therapy of Melanoma - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 10433619
AU - Autier P; Dore JF; Negrier S; Lienard D; Panizzon R; Lejeune FJ;
TI -
Guggisberg D; Eggermont AM
Sunscreen use and duration of sun exposure: a double-blind, randomized
trial.
SO - J Natl Cancer Inst 1999 Aug 4;91(15):1304-9
AD - Division of Epidemiology and Biostatistics, European Institute of
Oncology, Milan, Italy. pautier@ieo.it
BACKGROUND: In epidemiologic studies, sunscreen use is associated with
increased risk of cutaneous melanoma, basal cell skin cancer, and higher
numbers of nevi. It has been proposed that sunscreens may encourage
prolonged sun exposure because they delay sunburn occurrence. We
examined whether, under habitual conditions of sunscreen use, the
sun-protection factor (SPF) had an influence on sun-exposure duration.
METHODS: Before the 1997 summer holidays, we randomly assigned 87 French
and Swiss participants who were 18-24 years of age to receive an SPF 10
or an SPF 30 sunscreen. Neither medical personnel nor study participants
were aware of their sunscreen assignment. Participants were asked to
complete daily records of their sun exposure. To avoid influencing the
recreational sun-exposure habits of the study participants, no
recommendation was made about sun exposure or sun protection.
Furthermore, participants were told that the trial end point was the
number of pigmented skin lesions before and after the holidays. One
subject was lost to follow-up. All statistical tests were two-sided.
RESULTS: The SPF 10 (n = 44) and SPF 30 (n = 42) groups had equivalent
mean holiday durations (19.4 days versus 20.2 days) and mean quantities
of sunscreen used (72.3 g versus 71.6 g). The mean cumulative sun
exposures for the two groups were 58.2 hours and 72.6 hours,
respectively (P =.011). The mean daily durations of sunbathing were 2.6
and 3.1 hours, respectively (P =.0013), and, for outdoor activities,
they were 3.6 and 3.8 hours, respectively (P =.62). There was no
difference in sunburn experience between the two groups. CONCLUSIONS:
Use of higher SPF sunscreen seems to increase the duration of
recreational sun exposure of young white Europeans.
2
UI - 11642609
AU - Jean D; Bar-Eli M
TI -
Targeting the ATF-1/CREB transcription factors by single chain Fv
fragment in human melanoma: potential modality for cancer therapy.
SO - Crit Rev Immunol 2001;21(1-3):275-86
AD - Department of Cancer Biology, The University of Texas M. D. Anderson
Cancer Center, Houston 77030, USA.
Activating transcription factor-1 (ATF-1) and cAMP-responsive element
(CRE)-binding protein (CREB) have been implicated in cAMP and
Ca2+-induced transcriptional activation. The expression of the
transcription factors ATF-1 and CREB is upregulated in metastatic
melanoma cells. However, how overexpression of ATF-1/CREB contributes to
the acquisition of the metastatic phenotype is unclear. Previously we
demonstrated that quenching of CREB activity in metastatic melanoma
cells by means of a dominant-negative form of CREB (KCREB) led to a
decrease in their tumorigenicity and metastatic potential in nude mice.
We identified two mechanisms that explain how overexpression of
CREB/ATF-1 contributes to the metastatic phenotype. The first is one in
which CREB/ATF-1 play an essential role in invasion by regulating the
CRE-dependent expression of the metalloproteinase MMP-2 and the adhesion
molecule MCAM/MUC18 genes. In the second mechanism, CREB and ATF-1 act
as survival factors for human melanoma cells. Here, the effect of
disrupting ATF-1 activity was investigated using intracellular
expression of an inhibitory anti-ATF-1 single chain antibody fragment
(ScFv). Intracellular expression of ScFv anti-ATF-1 in MeWo melanoma
cells caused significant reduction in CRE-dependent promoter activation.
In addition, expression of ScFv anti-ATF-1 in melanoma cells suppressed
their tumorigenicity and metastatic potential in nude mice. ScFv
anti-ATF-1 rendered the melanoma cells susceptible to
thapsigargin-induced apoptosis in vitro and caused massive apoptosis in
tumors transplanted subcutaneously into nude mice, confirming that
AFT-1/CREB act as survival factors for human melanoma cells. These
studies demonstrate the potential usage of ScFv anti-ATF-1 as an
inhibitor of tumor growth and metastasis of solid tumors in vivo.
3
UI - 11857313
AU - Gutman H; Schachter J; Stopel E; Gutman R; Lahav J
TI -
Impaired platelet aggregation in melanoma patients treated with
interferon-alpha-2b adjuvant therapy.
SO - Cancer 2002 Feb 1;94(3):780-5
AD - Department of Surgery B, Rabin Medical Center, Beilinson Campus, Petah
Tiqva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv,
Israel. hgutman@clalit.org.il
BACKGROUND: High-dose interferon (INF)- alpha-2b is the only Food and
Drug Administration-approved adjuvant treatment for patients with
melanoma who are at high risk of recurrence. Although circumstantial
evidence points to a potentially harmful effect of INF-alpha-2b on
platelet function, to the authors' knowledge this has never been studied
in humans. METHODS: The study group was comprised of patients who had
undergone surgery for melanoma and were free of disease but at a high
risk of recurrence. All patients were candidates for adjuvant INF
treatment (high-dose) and were undergoing routine evaluation to which
platelet aggregation was added. Aggregation was triggered in standard
fashion with adenosine diphosphate, epinephrine, collagen, thrombin,
arachidonic acid, and ristocetin. Blood samples were drawn immediately
before treatment, during the intravenous loading phase, during the
subcutaneous maintenance phase, and 3-6 weeks after cessation of
treatment. Patients receiving low-dose, long-standing INF-alpha-2b
treatment also were tested. All results at each phase were compared with
those of normal controls. RESULTS: In those patients receiving high-dose
INF-alpha-2b, ristocetin-induced aggregation did not appear to be
affected. However, the response to > or = 1 of the other agonists was
impaired in 5 of 6 samples during loading, 14 of 15 samples during the
maintenance phase, and 8 of 13 samples after treatment, compared with
only 1 of 8 samples before treatment (P = 0.025, P = 0.002, and P =
0.067, respectively). During treatment with low-dose INF, platelet
function was affected to a lesser extent. CONCLUSIONS: INF treatment in
melanoma patients appears to be associated with severe impairment of
platelet aggregation, which appears to be dose-dependent and
cumulative-dose-dependent. This is not detectable by the standard
coagulation profile. This effect has significant implications in the
event of accidental injury or elective surgery. The antiaggregation
activity may be the mechanism by which INF delays, reduces, or prevents
the formation of melanoma metastases. Copyright 2002 American Cancer
Society. DOI 10.1002/cncr.10261
4
UI - 11565830
AU - Schwartzentruber DJ
TI -
Guidelines for the safe administration of high-dose interleukin-2.
SO - J Immunother 2001 Jul-Aug;24(4):287-93
AD - Surgery Branch, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland 20892, USA. djs@nih.gov
High-dose interleukin-2 (IL-2) results in objective clinical regression
of metastatic cancer in 15% to 17% of patients with melanoma and renal
cell carcinoma. Durable complete regression of all metastases is seen in
6% to 8% of patients. Based on these findings, the U.S. Food and Drug
Administration has approved the use of high-dose IL-2 for the treatment
of patients with metastatic melanoma and renal cell carcinoma.
Interleukin-2 administration is associated with many different side
effects, and after many years of use, clinicians have learned how to
safely administer high-dose IL-2. This article details practical
guidelines for the safe administration of high-dose IL-2.
5
UI - 11565838
AU - Dudley ME; Wunderlich J; Nishimura MI; Yu D; Yang JC; Topalian SL;
TI -
Schwartzentruber DJ; Hwu P; Marincola FM; Sherry R; Leitman SF;
Rosenberg SA
Adoptive transfer of cloned melanoma-reactive T lymphocytes for the
treatment of patients with metastatic melanoma.
SO - J Immunother 2001 Jul-Aug;24(4):363-73
AD - Surgery Branch, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland 20892-1502, USA. mark_dudley@nih.gov
This report describes a phase I study of the adoptive transfer of cloned
melanoma antigen-specific T lymphocytes for therapy of patients with
advanced melanoma. Clones were derived from peripheral blood lymphocytes
or tumor-infiltrating lymphocytes of patients who had received prior
immunization with the melanoma-associated antigen, gpl00. In response to
its cognate antigen, each clone used for treatment secreted large
amounts of interferon-gamma and granulocyte-macrophage
colony-stimulating factor, lesser amounts of interleukin (IL)-2 and
tumor necrosis factor-alpha, and little or no IL-4 and IL-10. Clones
also demonstrated recognition of human leukocyte antigen-matched
melanomas using cytokine secretion and lysis assays. Twelve patients
received 2 cycles of cells alone; 11 patients received additional cycles
of cells and were randomized between two schedules of IL-2 (125,000
IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg
intravenously every 8 h for 4 days). A total of 51 cycles of cells were
administered, with an average of 1 x 10(10) cells per cycle. Peripheral
blood samples were analyzed for persistence of transferred cells by
T-cell receptor-specific polymerase chain reaction. Transferred cells
reached a maximum level at 1 h after transfer but rapidly declined to
undetectable levels by 2 weeks. One minor response and one mixed
response were observed (both in the high-dose IL-2 arm). This report
demonstrates the safety and feasibility of cloned T-cell transfer as a
therapy for patients with cancer. The lack of clinical effectiveness of
this protocol suggests that transfer of different or additional cell
types or that modulation of the recipient host environment is required
for successful therapy.
6
UI - 11561695
AU - Margolin K; Longmate J; Synold TW; Gandara DR; Weber J; Gonzalez R;
TI -
Johansen MJ; Newman R; Baratta T; Doroshow JH
Dolastatin-10 in metastatic melanoma: a phase II and pharmokinetic trial
of the California Cancer Consortium.
SO - Invest New Drugs 2001;19(4):335-40
AD - Department of Medical Oncology and Therapeutics Research, City of Hope
National Medical Center, Duarte, CA 91010, USA. kmargolin@coh.org
Dolastatin-10 is a novel pentapeptide agent originally isolated from the
marine mollusk Dolabella auricularia with a mechanism of antitumor
activity that involves the inhibition of microtubule assembly. We
performed a Phase II trial of Dolastatin-10, 400 microg/m2 in patients
with advanced melanoma who had received no prior chemotherapy.
Dolastatin-10 pharmokinetics were evaluated in a subset of patients
following courses 1 and 2. Twelve patients were treated with a median of
2 cycles of Dolastatin-10, and no patient experienced an objective
response. The only grade >2 toxicities were grade 3 neutropenia
uncomplicated by infection, occurring in 4 patients following the first
treatment cycle. The total systemic clearance and volume of distribution
at steady-state were 2.61 +/- 1.9 L/h/m2 and 28.4 +/- 13 L/m2,
respectively. Due to prolonged terminal elimination. Dolastatin-10
plasma concentrations of greater than 1 nM were sustained for 24 h in
all patients studied. Dolastatin-10 is unlikely to have substantial
activity in the treatment of melanoma.
7
UI - 11870502
AU - Atzpodien J; Neuber K; Kamanabrou D; Fluck M; Brocker EB; Neumann C;
TI -
Runger TM; Schuler G; von den Driesch P; Muller I; Paul E; Patzelt T;
Reitz M
Combination chemotherapy with or without s.c. IL-2 and IFN-alpha:
results of a prospectively randomized trial of the Cooperative Advanced
Malignant Melanoma Chemoimmunotherapy Group (ACIMM).
SO - Br J Cancer 2002 Jan 21;86(2):179-84
AD - European Institute for Tumor Immunology and Prevention (EUTIP),
Gotenstr. 152, 53175 Bonn, Germany. SekrProfAtzpodien@yahoo.de
The purpose of this randomized trial was to evaluate the efficacy of
combination chemoimmunotherapy compared with chemotherapy alone. A total
of 124 patients were randomized to receive intravenous cisplatin (35 mg
m(-2), days 1-3), carmustine (150 mg m(-2), day 1, cycles 1 and 3 only),
dacarbacine (220 mg m(-2), days 1-3) and oral tamoxifen (20 mg m(-2),
daily) in combination with (n=64) or without (n=60) sequential
subcutaneous IL-2 and IFN-alpha. In those patients who received
sequential immunotherapy, each cycle of chemotherapy was followed by
outpatient s.c. IL-2 (10 x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6)
IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2),
day 1, week 4; days 1, 3, 5, week 5). The overall response rate of
patients treated with the combination of chemotherapy and IL-2/IFN-alpha
was 34.3% with seven complete responses (10.9%) and 15 partial responses
(23.4%). In patients treated with chemotherapy, only, the overall
response rate was 29.9% with eight complete responses (13.3%) and 10
partial responses (16.6%). There was no significant difference in median
progression free survival (0 months vs 4 months) and in median overall
survival (12 months vs 13 months) for combined chemoimmunotherapy and
for chemotherapy, respectively. Copyright 2002 The Cancer Research
Campaign
8
UI - 11841361
AU - Roberts DL; Anstey AV; Barlow RJ; Cox NH; Newton Bishop JA; Corrie PG;
TI -
Evans J; Gore ME; Hall PN; Kirkham N; The British Association of
Dermatologists; The Melanoma Study Group
U.K. guidelines for the management of cutaneous melanoma.
SO - Br J Dermatol 2002 Jan;146(1):7-17
AD - Singleton Hospital, Swansea SA2 8QA, UK.
These guidelines for management of cutaneous melanoma present
evidence-based guidance for treatment, with identification of the
strength of evidence available at the time of preparation of the
guidelines, and a brief overview of epidemiological aspects, diagnosis
and investigation. To reflect the collaborative process for the U.K.,
they are subject to dual publication in the British Journal of
Dermatology and the British Journal of Plastic Surgery.
9
UI - 11786569
AU - Bafaloukos D; Gogas H; Georgoulias V; Briassoulis E; Fountzilas G;
TI -
Samantas E; Kalofonos Ch; Skarlos D; Karabelis A; Kosmidis P
Temozolomide in combination with docetaxel in patients with advanced
melanoma: a phase II study of the Hellenic Cooperative Oncology Group.
SO - J Clin Oncol 2002 Jan 15;20(2):420-5
AD - Metaxa's Cancer Hospital, Piraeus, Greece. hesmo@compulink.gr
PURPOSE: Temozolomide is a novel oral alkylating agent that is effective
against melanoma. Moreover, temozolomide readily crosses the blood-brain
barrier and may consequently be effective in patients with brain
metastases. This phase II study was performed to assess the efficacy and
safety of the combination regimen of temozolomide and docetaxel in
patients with advanced metastatic melanoma. PATIENTS AND METHODS:
Sixty-five patients with metastatic melanoma were enrolled. Treatment
consisted of intravenous docetaxel (80 mg/m(2)) on day 1 and oral
temozolomide (150 mg/m(2)) on days 1 to 5, every 4 weeks, for a maximum
of six cycles. RESULTS: Sixty-two patients were eligible for the
efficacy and safety analysis. Seventeen patients (27%) achieved an
objective response, including five complete (8%) and 12 partial
responses (19%). Median response duration was 9.5 months. Among
responders, median time to progression (TTP) was 11.2 months and median
overall survival (OS) was 16 months. For all treated patients, the
median TTP was 4 months and median OS was 11 months. Three (38%) of
eight patients who presented with brain metastases had a partial
response for 5, 6, and 12 months. Of 52 patients who did not have brain
involvement at presentation, only four (8%) developed brain metastases
at a median follow-up of 14 months. Myelosuppression was the primary
toxicity. CONCLUSION: The combination of temozolomide and docetaxel was
effective and well tolerated as first-line treatment for patients with
advanced metastatic melanoma and demonstrated encouraging antitumor
activity against brain metastases.
10
UI - 11824246
AU - Meyer T; Gohl J
TI -
[Regional chemotherapy--perfusion of the extremities]
SO - Kongressbd Dtsch Ges Chir Kongr 2001;118():200-4
AD - Chirurgische Universitatsklinik Erlangen, Krankenhausstrasse 12, 91054
Erlangen.
Hyperthermic isolated limb perfusion with cytostatic drugs (HILP) is
indicated in locoregional recurrences of malignant melanoma of the
limbs. As a neoadjuvant treatment it is also used for non-curatively
resectable soft tissue sarcoma or their recurrences on the extremities.
Up to now, melphalan is still the standard drug in HILP for malignant
melanoma. With melphalan, complete response can be achieved in 65-80%
for clinically detectable in transit metastases (+/- regional lymph node
metastases). The combination of tumor necrosis factor (TNF) alpha with
melphalan has considerably improved response rates of HILP in sarcoma.
In more than 80% of the patients the otherwise necessary amputation of
the limb can be avoided. The combination of TNF with other drugs than
melphalan could possibly further improve results of HILP in sarcoma
patients. The high rate of local recurrences of malignant melanoma after
HILP poses an unsolved problem yet.
11
UI - 11899132
AU - Kaskel P
TI -
Why ultraviolet protection with clothing makes sense.
SO - Br J Dermatol 2001 Dec;145(6):1030
12
UI - 11869699
AU - Guadagni S; Russo F; Rossi CR; Pilati PL; Miotto D; Fiorentini G; Deraco
TI -
M; Santinami M; Palumbo G; Valenti M; Amicucci G
Deliberate hypoxic pelvic and limb chemoperfusion in the treatment of
recurrent melanoma.
SO - Am J Surg 2002 Jan;183(1):28-36
AD - Department of Surgical Sciences, University of L'Aquila, 67010 L'Aquila,
Italy. stefanoguadagni@interfree.it
BACKGROUND: The treatment of patients with advanced or recurrent pelvic
melanoma, which are often associated with lesions in the lower limbs, is
still unsatisfactory and controversial. A simplified hypoxic pelvic and
limb perfusion has been recently recommended to provide therapeutic
options for palliation and possibly cure. METHODS: A nonrandomized and
noncontrolled phase II experimental study was performed in 11 patients
with symptomatic unresectable recurrent melanoma of the pelvis and limb.
Patients were submitted to hypoxic pelvic and limb perfusion with 25
mg/m(2) of melphalan, 50 mg/m(2) of cisplatin, 300 mg/m(2) of
dacarbazine, and 75 mg/m(2) of epirubicin by means of a simplified
balloon occlusion technique. Response rate and time to disease
progression were the primary endpoints; overall survival was the
secondary endpoint. RESULTS: During the procedures there were no
technical, hemodynamic, or vascular complications, and no deaths
occurred during surgery or in the postoperative period. Response rate
was 82% (95% confidence interval, 58% to 100%). Median time to disease
progression was 12 months (range 9 to 30 months). Three-year overall
survival was 34%. CONCLUSIONS: Hypoxic pelvic and limb perfusion is a
safe and good palliative treatment for patients with unresectable
recurrent melanoma. Further studies are necessary to to confirm these
data and to establish if refinements can be made with acceptable
toxicity.
13
UI - 11905697
AU - Howe M
TI -
Melanoma vaccine launch may be too early.
SO - Lancet Oncol 2000 Sep;1(1):9
14
UI - 11870551
AU - Prasmickaite L; Hogset A; Selbo PK; Engesaeter BO; Hellum M; Berg K
TI -
Photochemical disruption of endocytic vesicles before delivery of drugs:
a new strategy for cancer therapy.
SO - Br J Cancer 2002 Feb 12;86(4):652-7
AD - Department of Biophysics, Institute for Cancer Research, The Norwegian
Radium Hospital, Montebello, N-0310 Oslo, Norway.
lina.prasmickaite@labmed.uio.no
The development of methods for specific delivery of drugs is an
important issue for many cancer therapy approaches. Most of
macromolecular drugs are taken into the cell through endocytosis and,
being unable to escape from endocytic vesicles, eventually are degraded
there, which hinders their therapeutic usefulness. We have developed a
method, called photochemical internalization, based on light-induced
photochemical reactions, disrupting endocytic vesicles specifically
within illuminated sites e.g. tumours. Here we present a new drug
delivery concept based on photochemical internalization-principle --
photochemical disruption of endocytic vesicles before delivery of
macromolecules, leading to an instant endosomal release instead of
detrimental stay of the molecules in endocytic vesicles. Previously we
have shown that illumination applied after the treatment with
macromolecules substantially improved their biological effect both in
vitro and in vivo. Here we demonstrate that exposure to light before
delivery of protein toxin gelonin improves gelonin effect in vitro much
more than light after. However, in vitro transfection with reporter
genes delivered by non-viral and adenoviral vectors is increased more
than 10- and six-fold, respectively, by both photochemical
internalization strategies. The possible cellular mechanisms involved,
and the potential of this new method for practical application of
photochemical internalization concept in cancer therapy are discussed.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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