Table of Contents
1
UI - 21249764
AU - Wildemore JK 4th; Schuchter L; Mick R; Synnestvedt M; Elenitsas R;
TI -
Bedrosian I; Czerniecki BJ; Guerry D 4th; Lessin SR; Elder DE; Bucky LP
Locally recurrent malignant melanoma characteristics and outcomes: a
single-institution study.
SO - Ann Plast Surg 2001 May;46(5):488-94
AD - Department of Surgery, University of Pennsylvania Medical Center,
Philadelphia, USA.
Despite improvements in the identification and treatment of melanoma,
local recurrence continues to challenge the success of current melanoma
therapy. A retrospective analysis of 1,996 patients presenting from 1990
to 1997 at the Pigmented Lesion Group of the University of Pennsylvania
was performed to assess clinical characteristics and outcomes of locally
recurrent melanoma. The cases were analyzed by chart and pathological
slide review. A control group was identified for statistical comparison.
The incidence of locally recurrent melanoma during the study period was
2.2%. Lentigo maligna melanoma (LMM) accounted for 37% of the local
recurrences. Increased tumor thickness and microsatellites were
associated with "early" local recurrence and decreased survival from
time of recurrence. Nineteen percent of the local recurrences occurred
more than 5 years after the initial definitive treatment. The
preponderance of locally recurrent LMM suggests the need for refinements
in the techniques of margin identification and surgical excision of LMM.
Tumors with increased thickness and microsatellites should receive
particularly close attention. Lastly, with nearly 20% of the local
recurrences occurring more than 5 years after the initial date of
treatment, the authors suggest extending the follow-up time for all
melanoma lesions beyond 5 years.
2
UI - 21271574
AU - Ooi BS; Eu KW; Seow-Choen F
TI -
Primary anorectal malignant melanoma: clinical features and results of
surgical therapy in Singapore--a case series.
SO - Ann Acad Med Singapore 2001 Mar;30(2):203-5
AD - Department of Colorectal Surgery, Singapore General Hospital, 1 Hospital
Drive, Singapore 169608.
INTRODUCTION: Primary malignant melanoma arising from the anorectum is
uncommon. The natural history of anorectal malignant melanoma is that of
a very poor prognosis with early dissemination of disease. Successful
surgical treatment has been rare. The present series reviews the
clinical features and results of surgical management of patients with
anorectal malignant melanoma treated in the Department of Colorectal
Surgery, Singapore General Hospital. MATERIALS AND METHODS: Data for all
patients treated for anorectal malignant melanoma during an 11-year
period from 1989 to 1999 were reviewed. The age, sex, presenting
symptoms, duration of symptoms prior to diagnosis, size of tumour,
extent of disease, type of surgery and length of survival were analysed.
RESULTS: Four men and 2 women, ranging in age from 31 to 81 years with
histologically proven primary anorectal malignant melanoma, were
included in the study. The most common (67%) presenting symptom was
rectal bleeding. The mean tumour size was 2.5 cm (range 1 to 5 cm). All
underwent abdomino-perineal resection. Three died of disseminated
disease within 17 months while the other 3 were still alive at the time
of this study; the longest up to 6.5 years from the time of diagnosis.
CONCLUSION: The prognosis of primary anorectal malignant melanoma is
poor. However, it is worthwhile treating aggressively as long-term
survivor may be encountered in some.
3
UI - 21274616
AU - Weinberg JM; Silverberg NB
TI -
Stemming the tide.
SO - Cutis 2001 May;67(5):363
4
UI - 21274622
AU - Carucci JA
TI -
Treatment of lentigo maligna.
SO - Cutis 2001 May;67(5):389-92
AD - Department of Dermatology, Weill Medical College of Cornell University,
525 E 68th St, New York, NY 10021, USA.
Lentigo maligna (LM) is an indolent form of melanoma in situ with the
potential to progress to invasive melanoma. Early detection and adequate
treatment prior to development to invasive melanoma are essential.
Definitive excision with negative margins is currently the treatment of
choice for LM. Conventional excision, Mohs micrographic surgical
excision, and nonexcisional methods of treatment of LM will be
discussed.
5
UI - 21274623
AU - Silverberg NB
TI -
Update on malignant melanoma in children.
SO - Cutis 2001 May;67(5):393-6
AD - Department of Dermatology, St. Luke's-Roosevelt Hospital Center, 1090
Amsterdam Ave, Suite 11D, New York, NY 10025, USA. nsilverberg@slrhc.org
Malignant melanoma is a rare event in children. Yet, the overall
incidence has consistently risen in the past 20 years. Thus, the
likelihood that our pediatric patients will develop malignant melanoma
is increasing. Previously, the bulk of lesions were estimated to occur
in children with large congenital melanocytic nevi. Recent reports,
however, have highlighted new risk factors for malignant melanoma in
children, while demystifying other entities previously believed to have
a grave prognosis. Knowledge of risk factors and participation in public
health efforts toward prevention and early intervention can help the
practitioner protect pediatric patients from this malignancy.
6
UI - 21328265
AU - Tullio A; Bianchi B; Sesenna E
TI -
[Lymphatic metastases in the parotid region from malignant skin neoplasm
of the head: considerations for surgical treatment based on personal
clinical experience]
SO - Acta Otorhinolaryngol Ital 2001 Feb;21(1):44-9
AD - Cattedra e Divisione di Chirurgia Maxillo-Facciale, Universita ed
Ospedale di Parma.
The present paper considers some of the problems linked to the surgical
treatment of parotid metastases. The authors base these considerations
on their limited personal cases and on the most accredited literature.
In the presence of cutaneous malignancies of the upper portion of the
face, accurate clinical-radiological evaluation must be made of the
parotid and neck region. Elective parotidectomy is performed when the
cutaneous carcinoma is quite extensive or located in proximity of the
gland or when the case involves a melanoma. Depending on the oncological
margins, a sub-total parotidectomy may be enough; however, the facial
nerve must be sacrificed if there is a clinical deficit or if it is
directly affected by the tumor. As the dimensions of the neoplasm
increase, the feasibility of saving the nerve decreases. Prophylactic
treatment of the neck is advisable in parotid metastases from cutaneous
malignancies, particularly melanoma. Nevertheless, it is possible to
perform a selective dissection, avoiding the V level of the neck as the
incidence of its involvement is quite low. Prognosis for these tumors is
extremely poor. Of the eleven patients surgically treated, only 4 (36%)
survived: 2 passed away from other causes not involved in the base
pathology; 2 for distant metastases but with no signs of local
recurrence and 1 other for recurrence of the primary pathology in the
maxillary sinus mucosa. There is no difference in the survival of the
two main histological groups: 2 out of 3 of the patients with melanoma
(67%) died as did 3 out of 5 (60%) of those with epidermal carcinoma.
This does not, obviously, include the two patients who died from other
causes.
7
UI - 21367248
AU - Keiholz U; Scheibenbogen C; Theil E; Schadendorf D
TI -
Rational development of peptide vaccination in clinical oncology.
SO - Onkologie 2001 Apr;24(2):174
8
UI - 21439108
AU - Buzaid AC; Atkins M
TI -
Practical guidelines for the management of biochemotherapy-related
toxicity in melanoma.
SO - Clin Cancer Res 2001 Sep;7(9):2611-9
AD - Oncology Center, Hospital Sirio-Libanes, Sao Paulo, SP 01308-050,
Brazil. buzaid@attglobal.net
The combination of cisplatin-based chemotherapy with interleukin 2
(IL-2) and IFN-alpha, referred to as biochemotherapy or
chemoimmunotherapy, has shown promising antitumor activity in patients
with metastatic melanoma. Phase II studies have reported overall
response rates ranging from 40 to 60%, with durable complete remissions
in approximately 10% of the patients. Toxicity, however, is often severe
and can be life-threatening if the healthcare team is not familiar with
toxicity management. In this report, we briefly describe the clinical
results of the most effective biochemotherapy regimens and provide a
detailed description and management of the most common toxic effects,
with emphasis on the concurrent biochemotherapy program initially
developed at M. D. Anderson Cancer Center and currently being tested in
a slightly modified version in two large-scale Intergroup Phase III
trials.
9
UI - 21443206
AU - Dubois RW; Swetter SM; Atkins M; McMasters K; Halbert R; Miller SJ;
TI -
Shiell R; Kirkwood J
Developing indications for the use of sentinel lymph node biopsy and
adjuvant high-dose interferon alfa-2b in melanoma.
SO - Arch Dermatol 2001 Sep;137(9):1217-24
AD - Protocare Sciences Inc, Santa Monica, USA. dubois@zynx.com
OBJECTIVES: To convene a multidisciplinary panel of dermatologists,
surgical oncologists, and medical oncologists to formally review
available data on the sentinel lymph node (SLN) biopsy procedure and
high-dose adjuvant interferon alfa-2b therapy for patients with melanoma
and to rate the "appropriateness," "inappropriateness," or "uncertainty"
of the procedure and therapy to guide clinical decision making in
practice. PARTICIPANTS: The panel comprised 13 specialists (4
dermatologists, 4 oncologists, and 5 surgeons) from geographically
diverse areas who practiced in community-based settings (n = 8) and
academic institutions (n = 5). Participants were chosen based on
recommendations from the relevant specialty organizations. EVIDENCE: A
formal literature review was conducted by investigators at Protocare
Sciences Inc, Santa Monica, Calif, on the risks and benefits of
performing an SLN biopsy in patients with stage I or II melanoma and
adjuvant interferon alfa-2b therapy in patients with stage II or III
and supplemental information was obtained from various cancer societies
and cancer research groups. Panel participants were queried on
additional sources of relevant information. Unpublished, presented data
were included in abstract form on 1 recently closed clinical trial.
CONSENSUS PROCESS: The RAND/UCLA Appropriateness Method was used to
review and rate multiple clinical scenarios for the use of SLN biopsy
and interferon alfa-2b therapy. The consensus method did not force
agreement. CONCLUSIONS: The panel rated 104 clinical scenarios and
concluded that the SLN biopsy procedure was appropriate for primary
melanomas deeper than 1.0 mm and for tumors 1 mm or less when histologic
ulceration was present and/or classified as Clark level 4 or higher. The
SLN biopsy was deemed inappropriate for nonulcerated Clark level 2 or 3
melanomas 0.75 mm or less in depth and uncertain in tumors 0.76 to 1.0
mm deep unless they were ulcerated or Clark level 4 or higher.
Interferon alfa-2b therapy was deemed appropriate for patients with
regional nodal and/or in-transit metastasis and for node-negative
patients with primary melanomas deeper than 4 mm. The panel considered
the use of interferon alfa-2b therapy uncertain in patients with
ulcerated intermediate primary tumors (2.01-4.0 mm in depth) and
inappropriate for node-negative patients with nonulcerated tumors less
than 4.0 mm deep. Specialty-specific ratings were conducted as well.
10
UI - 21443825
AU - Lee P; Wang F; Kuniyoshi J; Rubio V; Stuges T; Groshen S; Gee C; Lau R;
TI -
Jeffery G; Margolin K; Marty V; Weber J
Effects of interleukin-12 on the immune response to a multipeptide
vaccine for resected metastatic melanoma.
SO - J Clin Oncol 2001 Sep 15;19(18):3836-47
AD - Department of Medicine, Division of Medical Oncology, Keck/University of
Southern California School of Medicine, Los Angeles, USA.
PURPOSE: Forty-eight patients with high-risk re-sected stage III or IV
melanoma were immunized with two tumor antigen epitope peptides derived
from gp100(209-217)(210M) (IMDQVPSFV) and tyrosinase(368-376)(370D)
(YMDGTMSQV) emulsified with incomplete Freund's adjuvant (IFA). Patients
received peptides/IFA with or without interleukin (IL)-12 30 ng/kg to
evaluate the toxicities and immune responses in either arm with time to
relapse and survival as secondary end points. PATIENTS AND METHODS:
Immunizations were administered every 2 weeks for 8 weeks, then every 4
weeks for 12 weeks, and then once 8 weeks later. A leukapheresis to
obtain peripheral-blood mononuclear cells for immune analyses was done
before and after vaccination. Skin testing with peptides and recall
reagents was performed before and after vaccinations. RESULTS: Local
pain and granuloma formation, fever, and lethargy of grade 1 or 2 were
observed. Transient vaccine-related grade 3-but no grade 4-toxicity was
observed. Thirty-four of 40 patients developed a positive skin test
response to the gp100 peptide but none to tyrosinase. Immune responses
were measured by release of gamma-interferon in an enzyme-linked
immunosorbent assay (ELISA) by effector cells in the presence of
peptide-pulsed antigen-presenting cells or by an antigen-specific
tetramer flow cytometry assay. Thirty-three of 38 patients demonstrated
an immune response by ELISA after vaccination, as did 37 of 42 patients
by tetramer assay. Twenty-four of 48 patients relapsed with a median
follow-up of 20 months, and 10 patients in this high-risk group have
died. CONCLUSION: These data suggest a significant proportion of
patients with resected melanoma mount an antigen-specific immune
response against a peptide vaccine and indicate that IL-12 may increase
the immune response and supporting further development of IL-12 as a
vaccine adjuvant.
11
UI - 21423023
AU - Kikuchi A; Nieda M; Schmidt C; Koezuka Y; Ishihara S; Ishikawa Y;
TI -
Tadokoro K; Durrant S; Boyd A; Juji T; Nicol A
In vitro anti-tumour activity of alpha-galactosylceramide-stimulated
human invariant Valpha24+NKT cells against melanoma.
SO - Br J Cancer 2001 Sep 1;85(5):741-6
AD - Department of Research, The Japanese Red Cross Central Blood Center,
4-1-31 Hiroo, Shibuya-ku, Tokyo, 150-0012, Japan.
alpha-galactosylceramide (KRN 7000, alpha-GalCer) has shown potent in
vivo anti-tumour activity in mice, including against melanoma and the
highly specific effect of inducing proliferation and activation of human
Valpha24+NKT-cells. We hypothesized that human Valpha24+NKT-cells
activated by alpha-GalCer might exhibit anti-tumour activity against
human melanoma. To investigate this, Valpha24+NKT-cells were generated
from the peripheral blood of patients with melanoma after stimulation
with alpha-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs).
Valpha24+NKT-cells did not exhibit cytolytic activity against the
primary autologous or allogeneic melanoma cell lines tested. However,
proliferation of the melanoma cell lines was markedly suppressed by
co-culture with activated Valpha24+NKT-cells (mean +/- SD inhibition of
proliferation 63.9 +/- 1.3%). Culture supernatants of activated
Valpha24+NKT-cell cultures stimulated with alpha-GalCer pulsed Mo-DCs
exhibited similar antiproliferative activities against melanoma cells,
indicating that the majority of the inhibitory effects were due to
soluble mediators rather than direct cell-to-cell interactions. This
effect was predominantly due to release of IFN-gamma, and to a lesser
extent IL-12. Other cytokines, including IL-4 and IL-10, were released
but these cytokines had less antiproliferative effects. These in vitro
results show that Valpha24+NKT-cells stimulated by alpha-GalCer-pulsed
Mo-DCs have anti-tumour activities against human melanoma through
antiproliferative effects exerted by soluble mediators rather than
cytolytic effects as observed against some other tumours. Induction of
local cytokine release by activated Valpha24+NKT-cells may contribute to
clinical anti-tumour effects of alpha-GalCer. Copyright 2001 Cancer
Research Campaign.
12
UI - 21468605
AU - Gonzalez-Larriba JL; Serrano S; Alvarez-Mon M; Camacho F; Casado MA;
TI -
Diaz-Perez JL; Diaz-Rubio E; Fosbrook L; Guillem V; Lopez-Lopez JJ;
Moreno-Nogueira JA; Toribio J
Cost-effectiveness analysis of interferon as adjuvant therapy in
high-risk melanoma patients in Spain.
SO - Eur J Cancer 2000 Dec;36(18):2344-52
AD - Department of Medical Oncology, Hospital Clinico San Carlos, Madrid,
Spain. joseg@ene.es
In the randomised clinical trial E1684, the administration of interferon
(IFN) alpha-2b resulted in prolonged disease-free and overall survival
in high-risk melanoma patients following surgical resection. However,
and considering the cost and toxicity of IFN, the convenience of its
widespread use should be evaluated. The aim of this study was to analyse
the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in
melanoma patients versus an untreated control group. A Markov model was
used to compare two hypothetical cohorts of 1000 patients aged 50 years,
according to the clinical outcome of the E1684 study. The cohort of
patients treated with IFN alpha-2b has an increased overall survival of
1.90 years during the patient's lifetime. The incremental discounted
cost per life year gained of IFN versus observation is 9015 Euros
according to the projection generated by the model. The sensitivity
analysis demonstrated that changes in the most relevant study end-points
do not modify the study outcome. In conclusion, in high-risk melanoma
patients following surgical resection, the cost-effectiveness of IFN
alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month,
followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an
untreated control group is within the limits established in health
economics to determine if adoption of a new treatment is economically
justified and is comparable with other interventions in which
cost-effectiveness is acceptable to the National Health System.
13
UI - 21190900
AU - Atkins MB; Redman B; Mier J; Gollob J; Weber J; Sosman J; MacPherson BL;
TI -
Plasse T
A phase I study of CNI-1493, an inhibitor of cytokine release, in
combination with high-dose interleukin-2 in patients with renal cancer
and melanoma.
SO - Clin Cancer Res 2001 Mar;7(3):486-92
AD - Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
CNI-1493, an inhibitor of proinflammatory cytokines, was studied in a
Phase I trial in melanoma and renal cancer patients receiving high-dose
interleukin 2 (IL-2). Objectives of the study were to define the maximum
tolerated dose (MTD) and toxicity of CNI-1493, to assess its
pharmacological effects, and to define its pharmacokinetics. Twenty-four
patients were treated in sequential cohorts with CNI-1493 doses from 2
through 32 mg/m2 daily. Patients first received only CNI-1493 daily for
5 days. After a 9-day rest, patients received two 5-day courses of IL-2
of 600,000 IU/kg every 8 h for up to 14 doses/course plus daily
CNI-1493; courses were separated by a 9-day rest period. CNI-1493
administered alone was well tolerated at doses through 32 mg/m2; MTD was
not reached. The only clinical toxicity attributed to CNI-1493 was
occasional injection-site phlebitis. Grade 1 creatinine increases
occurred in 1 of 7 patients at 4 mg/m2, in 1 of 1 patients at 25 mg/m2,
and in 3 of 6 patients at 32 mg/m2 CNI-1493 alone. In combination with
high-dose IL-2, CNI-1493 at > or = 25 mg/m2 seemed to exacerbate
IL-2-induced nephrotoxicity: grade 3 or 4 creatinine increases developed
in 3 of 6 patients at 25 or 32 mg/m2, as compared with 1 of 16 patients
at doses < or = 16 mg/m2. The MTD for CNI-1493 given with high-dose IL-2
was 16 mg/m2. The dose-limiting toxicity of IL-2 was hypotension in 63%
of patients; overall tolerance to IL-2 was not improved by CNI-1493.
However, relative to changes seen in a reference group receiving
high-dose IL-2 alone, at doses > or = 4 mg/m2 CNI-1493 did show evidence
of pharmacological activity as an inhibitor of tumor necrosis factor
production.
14
UI - 21262954
AU - Ribuffo D; Cavalieri L; De Vita F; Massa R; Prosperi D; Tuccimei M;
TI -
Scuderi N
Current role of immunoscintigraphy in malignant melanoma follow-up. A
study of 114 patients.
SO - J Exp Clin Cancer Res 2001 Mar;20(1):11-5
AD - Division of Plastic Surgery, Nuclear Medicine Section, La Sapienza
University, Rome, Italy.
Although its role and importance is debated, Immunoscintigraphy (IS)
remains a popular technique in Malignant Melanoma (MM) follow-up for
consecutive patients underwent 650 IS examinations at our Department.
follow-up of at least 7 years are given here. IS results were compared
to physical examination, to other imaging modalities and, where
available, to histology. IS specificity and sensivity, concerning
detection of melanoma metastases in lymph nodes, skin, brain, lung,
visceral sites and bone, ranged from 37.5% and 22% to 100%. Our results
indicate a high diagnostic accuracy of IS only for lymph node
examination, but not for other possible locations of melanoma
metastases. In our experience IS cannot be recommended for staging of
melanoma patients, and should only be used in association with other
imaging modalities.
15
UI - 21453549
AU - Lentsch EJ; Myers JN
TI -
Melanoma of the head and neck: current concepts in diagnosis and
management.
SO - Laryngoscope 2001 Jul;111(7):1209-22
AD - Department of Head and Neck Surgery, The University of Texas, M.D.
Anderson Cancer Center, Houston, Texas 77030, USA.
16
UI - 21424850
AU - Viar V
TI -
Advances in surgical treatment of melanoma.
SO - Nurs Clin North Am 2001 Sep;36(3):507-15, x
AD - Division of Surgical Oncology, Vanderbilt University Medical Center,
Nashville, Tennessee 37232, USA. vicki.viar@nortonhealthcare.org
Malignant melanoma is fatal in one-fifth of the patients who are
diagnosed with the disease. It is a solid tumor cancer that spreads
primarily through lymph nodes, making it amenable to surgical treatment.
Surgical interventions for melanoma that have developed over the years
include diagnostic biopsy, wide excision, lymph node staging, and
treatment of local and visceral metastases. Lymphatic mapping and
sentinel lymph node biopsy are two important surgical approaches that
are gaining favor over more traditional nodal staging. The use of
reverse transcriptase-polymerase chain reaction (RT-PCR) to diagnose
submicroscopic disease shows promise for staging patients at the
earliest possible time. Multicenter, randomized clinical trials such as
the Sunbelt Melanoma Trial are vital in answering the question of how
best to treat early metastatic melanoma.
17
UI - 21453500
AU - Cascinelli N; Belli F; MacKie RM; Santinami M; Bufalino R; Morabito A
TI -
Effect of long-term adjuvant therapy with interferon alpha-2a in
patients with regional node metastases from cutaneous melanoma: a
randomised trial.
SO - Lancet 2001 Sep 15;358(9285):866-9
AD - National Cancer Institute, Via G Venezian 1, 20133, Milan, Italy.
who-melanoma@istitutotumori.mi.it
BACKGROUND: Less than half of patients with melanoma that has spread to
local draining regional lymph nodes (stage III melanoma) live with no
disease for 5 years or longer after surgery. We aimed to see whether
interferon alpha-2a increased survival prospects in these patients.
METHODS: 444 patients from 23 centres in the WHO Melanoma Programme had
complete lymphadenectomy for pathologically proven regional nodal spread
of melanoma and were randomly assigned to receive either 3 MU
subcutaneously of recombinant interferon alpha-2a three times a week for
3 years, or to observation alone after surgery. Patients were stratified
by centre, nodes with macroscopic or microscopic melanoma, number of
affected nodes, and nodal metastatic spread. Treatment was continued for
3 years or until first sign of relapse. FINDINGS: 424 patients entered
the study. 5-year disease-free survival of those who had surgery plus
interferon alpha-2a was 27.5% (95% CI 21.7-33.6); for those who received
surgery alone, survival was 28.4% (22.5-34.6) (p=0.50). Neither
Kaplan-Meier cumulative survival rates, nor multivariate analysis of
survival, showed a difference between those who had surgery and
interferon alpha-2a (35%, 95% CI 29-42) and those who had surgery alone
(37%, 31-44). INTERPRETATION: Patients with melanoma that has spread to
the local draining regional lymph nodes tolerate well 3 MU of interferon
alpha-2a given subcutaneously three times a week for 3 years, but this
treatment does not improve either disease-free or overall survival.
18
UI - 21460579
AU - Smith C; Cerundolo V
TI -
Immunotherapy of melanoma.
SO - Immunology 2001 Sep;104(1):1-7
AD - Institute of Molecular Medicine, Nuffield Department of Medicine,
University of Oxford, Oxford, UK.
19
UI - 21298909
AU - Fusaro RM
TI -
Multiple interpretations of cancer risks from body mole counts in
preventive care.
SO - Arch Dermatol 2001 Jun;137(6):823
20
UI - 20208343
AU - Scheibenbogen C; Schmittel A; Keilholz U; Allgauer T; Hofmann U; Max R;
TI -
Thiel E; Schadendorf D
Phase 2 trial of vaccination with tyrosinase peptides and
granulocyte-macrophage colony-stimulating factor in patients with
metastatic melanoma.
SO - J Immunother 2000 Mar-Apr;23(2):275-81
AD - Universitatsklinikum Benjamin-Franklin, Medizinische Klinik III
(Hamatologie, Onkologie and Transfusionsmedizin), Freie Universitat
Berlin, Germany.
This phase II study was performed to determine the induction of a
specific T-cell response, the clinical response rate, and toxicity of
vaccination with different HLA class I-binding peptide epitopes derived
from the melanocyte differentiation antigen tyrosinase in patients with
stage IV melanoma. The study population consisted of 16 patients with
metastatic disease and two patients who were macroscopically free of
disease at study entry after resection of recurrent skin lesions.
Patients received intradermal injections of 200 microgram [corrected]
peptide corresponding to their HLA type on day 3, and 75 or 150 microg
granulocyte-macrophage colony-stimulating factor on days 1 to 4.
Vaccinations were repeated at weeks 2, 4, 6, 10, and 14. Monitoring of
peptide-specific T-cell frequencies in the peripheral blood was
performed using an interferon gamma ELISPOT assay. Eleven of the 16
patients with metastatic disease went off the protocol within the first
10 weeks because of tumor progression. Of the five patients with
metastatic disease who received all six vaccinations, one patient showed
a mixed response with regression of some lung metastases; two patients
with progressive disease before vaccination had stable disease for 6 and
18+ months; and two patients had progression of their disease. The two
patients who had all their metastases resected before vaccination did
not have relapses for 6 and 12+ months after vaccination. Induction of
tyrosinase-reactive T cells was found in these two patients and in two
others with metastatic disease, including the one who achieved a mixed
response and one with stable disease. This study shows limited clinical
and immunologic activity of HLA class 1-peptide vaccination in
combination with granulocyte-macrophage colony-stimulating factor in
stage IV melanoma patients.
21
UI - 21369211
AU - Bondar' GV; Psaras GG; Zolotukhin SE
TI -
[Treatment of colonic melanoma]
SO - Klin Khir 2001 Jan;(1):38-40
The results of treatment of 5 patients with colonic melanoma are
presented. Fine-needle biopsy was used for morphological verification
diagnosis. It was established that the patients with colonic melanoma
are hospitalized in specialized department, as a rule, with nonopertable
tumor. In 1 patient explorative laparotomy was done. Conduction of
radical operative intervention was impossible because of presence of
multiple metastases in liver. In 4 patients conservative treatment was
performed. It was not possible to perform radical operation because of
the process spreading. The patients life span after conduction of
conservative therapy have constituted 14.5 mo at average.
22
UI - 21372390
AU - Guven K; Kittler H; Wolff K; Pehamberger H
TI -
Cisplatin and carboplatin combination as second-line chemotherapy in
dacarbazine-resistant melanoma patients.
SO - Melanoma Res 2001 Aug;11(4):411-5
AD - Division of General Dermatology, Department of Dermatology, University
of Vienna Medical School, Wahringer Gurtel 18-20, A-1090 Vienna,
Austria. hubert.pehamberger@akh-wien.ac.at
High-dose cisplatin regimens have been shown to be highly active in
advanced melanoma patients but are associated with unacceptable side
effects. In order to increase the platinum dose but avoid severe side
effects, we treated 15 dacarbazine (DTIC)-resistant metastatic melanoma
patients with a combination regimen of cisplatin (100 mg/m2) and
carboplatin (200 mg/m2), two platinum analogues with a similar mode of
action but a different toxicity pattern. After a mean follow-up period
of 10.7 months (range 4-18 months), two patients (13.3%) achieved
complete remission and two patients (13.3%) showed partial remission,
giving an overall response rate of 26.4% (95% confidence interval [CI]
4.2-49%). Furthermore, three patients (20%; 95% CI 0-40.2%) experienced
stable disease. The median duration of response was 7.1 months (95% CI
4.2-10.0 months), and the median overall survival was 12.5 months (95%
CI 5.8-19.2 months), with eight patients still alive. The main side
effects were haematological (leukopenia/thrombocytopenia World Health
Organization [WHO] grade I-IV; anaemia WHO grade I-III),
gastrointestinal (WHO grade I-III), neurological (WHO grade I-II) and
renal (WHO grade I) toxicity. Nevertheless, except in one patient, side
effects did not result in discontinuation of therapy. Despite the small
number of patients treated in this preliminary study, we believe that
combining cisplatin and carboplatin represents a novel, active and
well-tolerated therapeutic option as second-line chemotherapy in
DTIC-resistant advanced melanoma patients.
23
UI - 21381723
AU - Stopeck AT; Jones A; Hersh EM; Thompson JA; Finucane DM; Gutheil JC;
TI -
Gonzalez R
Phase II study of direct intralesional gene transfer of allovectin-7, an
HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with
metastatic melanoma.
SO - Clin Cancer Res 2001 Aug;7(8):2285-91
AD - Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724,
USA. astopeck@azcc.arizona.edu
Cutaneous melanoma is one of the most rapidly increasing cancers in the
United States. Because of the lack of effective treatment options and
toxicities of most chemotherapeutic and radiation regimes,
immunotherapies such as vaccination therapy represent an attractive
approach for patients with advanced melanoma. The purpose of this study
was to evaluate the response rate, time to progression, and survival of
patients with metastatic melanoma treated by direct intratumoral
injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and
beta2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE.
Fifty-two patients with metastatic melanoma were enrolled in this Phase
II study. Therapy consisted of six intratumoral injections of 10 microg
of Allovectin-7 over a 9-week period. Treatment was well tolerated.
Treatment-related adverse events were mild to moderate, the most
frequent of which were ecchymosis, pruritus (and/or discomfort at the
injection site), and pneumothoraces. Regression of the injected lesion
was observed in 18% of patients, including one complete response, three
partial responses, and five minor responses. An overall response rate of
4% (two partial responses) was documented, and nine patients (18%)
maintained stable disease for at least 11 weeks. Six patients remained
alive 25.1 to 39.4 months from their first injection, including two
patients with local (injected tumor) responses and one patient with an
overall disease partial response. This study demonstrates that
intratumoral administration of Allovectin-7 in metastatic melanoma is
safe and can produce both responses in injected lesions and in overall
disease. Clinical trials optimizing patient selection and combining
Allovectin-7 with other modalities of therapy are currently ongoing in
an effort to improve response rates.
24
UI - 21426655
AU - Wolf R; Wolf D; Morganti P; Ruocco V
TI -
Sunscreens.
SO - Clin Dermatol 2001 Jul-Aug;19(4):452-9
AD - Department of Dermatology, Tel-Aviv Sourasky Medical Center, and the
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
wolf_r@netvision.net.il
25
UI - 21453198
AU - Sober AJ; Chuang TY; Duvic M; Farmer ER; Grichnik JM; Halpern AC; Ho V;
TI -
Holloway V; Hood AF; Johnson TM; Lowery BJ; The Guidelines/Outcomes
Committee
Guidelines of care for primary cutaneous melanoma.
SO - J Am Acad Dermatol 2001 Oct;45(4):579-86
26
UI - 21466976
AU - Konjevic G; Jovic V; Radulovic S; Jelic S; Dzodic R; Spuzic I
TI -
Therapeutic implications of the kinetics of immunomodulation during
single or combined treatment of melanoma patients with dacarbazine and
interferon-alpha.
SO - Neoplasma 2001;48(3):175-81
AD - Institute for Oncology and Radiology of Serbia, Belgrade, Yugoslavia.
The therapy of metastatic melanoma has not given satisfactory results.
Single chemo- or immunotherapeutic agents in the adjuvant setting or
combined chemoimmunotherapy for metastatic disease have generally been
evaluated only in terms of clinical benefit. Considering that
dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most
frequently used agents in the treatment of melanoma, the aim of this
study was to evaluate the kinetics of immunological changes during
adjuvant treatment of melanoma patients with DTIC or with IFN-alpha
monotherapy, as well as by their combination in metastatic disease. The
evaluated immunological parameters showed significant early increase in
the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell
number in patients treated with combined chemoimmunotherapy and an
increase in expression of the early activation antigen CD38 on CD8+
cytotoxic T cells, both, in patients treated with combined
chemoimmunotherapy and with IFN-alpha alone, while, no significant
change in any one parameter was detected in the group of patients
receiving DTIC. The kinetics of the observed immunological changes,
restricted to combined chemoimmunotherapy, indicate that the engagement
of antitumor immune response appears early but is short-lived and that
this favorable effect should be augmented and prolonged by the timely
introduction of additional immunomodulating agents.
27
UI - 20212767
AU - Brinckerhoff LH; Thompson LW; Slingluff CL Jr
TI -
Melanoma vaccines.
SO - Curr Opin Oncol 2000 Mar;12(2):163-73
AD - University of Virginia Health System, Department of Surgery,
Charlottesville 22908, USA.
Remarkable advances in tumor vaccination have been made since Coley
first deliberately infected cancer patients with both live and
heat-killed bacteria. Melanoma is the most immunogenic solid tumor and,
as such, has served as the major model for tumor vaccine investigation
in both the laboratory and the clinic. Many advances in the field of
melanoma vaccination have been based on an improved understanding of the
cellular interaction required to induce a specific antitumor immune
response. As a result of this new knowledge, many clinical trials of
melanoma vaccines are now under way, and vaccines for metastatic
melanoma have shown evidence of clinical effectiveness. This paper
outlines the current status of melanoma vaccination.
28
UI - 21300162
AU - Sondak VK; Chang AE
TI -
Treating colon cancer with a melanoma vaccine? Preposterous?
SO - Ann Surg Oncol 2001 Jun;8(5):386-8
29
UI - 21341684
AU - Livingston P
TI -
The unfulfilled promise of melanoma vaccines.
SO - Clin Cancer Res 2001 Jul;7(7):1837-8
30
UI - 21341692
AU - Bystryn JC; Zeleniuch-Jacquotte A; Oratz R; Shapiro RL; Harris MN; Roses
TI -
DF
Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine.
SO - Clin Cancer Res 2001 Jul;7(7):1882-7
AD - Ronald O. Perelman Department of Dermatology, Kaplan Comprehensive
Cancer Center, New York University School of Medicine, New York, New
York 10016, USA. bystryn@is.nyu.edu
A polyvalent melanoma vaccine prepared from shed antigens stimulates
humoral and cellular immune responses and improves survival compared
with historical controls. We conducted a double-blind, prospectively
randomized, placebo-controlled trial to assess whether this vaccine
could slow the progression of resected melanoma. Thirty-eight patients
with resected melanoma metastatic to regional nodes (American Joint
Committee on Cancer stage III) who had a particularly poor prognosis on
the basis of the nodes being clinically positive or two or more
histologically positive nodes were randomly assigned in a 2:1 ratio to
treatment with 40 microg of melanoma or placebo (human albumin) vaccine,
both of which were bound to alum as an adjuvant. Immunizations were
given intradermally into the extremities every 3 weeks x 4, monthly x 3,
every 3 months x 2, and then every 6 months for 5 years or until disease
progression. Twenty-four patients were treated with the melanoma, and 14
patients were treated with the placebo vaccine. The groups were evenly
balanced with respect to prognostic factors. Median length of
observation was 2.5 years. There was no local or systemic toxicity. By
Kaplan-Meier analysis, median time to disease progression was two and a
half times longer in patients treated with melanoma vaccine compared
with that in patients treated with placebo vaccine, i.e., 1.6 years (95%
confidence interval, 1.0-3.0 years) compared with 0.6 year [95%
confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards
analysis, this difference was significant at P = 0.03. Overall survival
was 40% longer in the melanoma vaccine-treated group (median overall
survival of 3.8 years versus 2.7 years), but this difference was not
statistically significant. In a double-blind and placebo-controlled
trial, these results suggest that immunization with a melanoma vaccine
may be able to slow the progression of melanoma. Although statistically
significant, these results must be interpreted with caution because they
are based on a small number of patients.
31
UI - 21476737
AU - Hudson LD
TI -
Melanoma 2001.
SO - South Med J 2001 Sep;94(9):851-2
32
UI - 21291617
AU - Smyth J; Boneterre ME; Schellens J; Calvert H; Greim G; Wanders J;
TI -
Hanauske A; EORTC Early Clinical Studies Group
Activity of the dolastatin analogue, LU103793, in malignant melanoma.
SO - Ann Oncol 2001 Apr;12(4):509-11
AD - ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
j.smyth@icrf.icnet.uk
LU103793, a synthetic analogue of dolastatin 15, showed interesting
pre-clinical activity in melanoma xenografts. In this phase II
multicentre trial, 80 chemotherapy-naive patients with metastatic
melanoma received a total of 218 cycles of treatment. The response rate
showed one complete and three partial responses of median duration six
months (range 3-9.1). Toxicity was moderate, mostly haematological
(neutropenia grade 4 in 16%, grade 3 in 3%). There were no significant
problems with hypertension or other non-haematological toxicities.
33
UI - 21325280
AU - Kristjansson S; Helgason AR; Rosdahl I; Holm LE; Ullen H
TI -
Readiness to change sun-protective behaviour.
SO - Eur J Cancer Prev 2001 Jun;10(3):289-96
AD - Department of Cancer Prevention, Stockholm Center of Public Health,
Karolinska Hospital, Sweden. sveinbjorn.kristjansson@smd.sll.se
The incidence of malignant melanoma and non-melanoma skin cancers has
increased rapidly in Sweden during the last 20 years. The best-known way
to revert this trend is primary prevention. Matching health messages to
readiness to change in the population may enhance the effect of
community-based prevention. The aims of this study were to investigate
readiness to change sun-protective behaviour in two groups (visitors to
mobile screening units and beach-goers) and to test a single-item
algorithm in assessing the stage of change in sun-protective behaviour.
Seven hundred and forty-two visitors to the mobile screening units and
202 individuals on nearby beaches answered a short questionnaire. The
assessment of readiness to change was based on stages of change in
sun-protective behaviour modified from the Transtheoretical Model of
Behaviour Change. As expected, the visitors to the screening units were
more often in action/maintenance stages than the beach group for most
sun-protective behaviours. In conclusion, the single-item algorithm
method appears to be sensitive to assess readiness to change
sun-protective behaviour, based on the Transtheoretical Model of
Behaviour Change. This method can be incorporated into population
surveys and may aid in developing successful skin cancer prevention
programmes.
34
UI - 21367186
AU - Kropp J; Stein A; Hackert I; Sebastian G; Meurer M; Gruning T; Liepe K;
TI -
Pinkert J; Franke WG
Accuracy of the intra-operative radioguided localization of the sentinel
lymph node (SLN) 24 hours after lymphoscintigraphy in patients with
malignant melanoma.
SO - Nuklearmedizin 2001 Jun;40(3):86-90
AD - Department of Nuclear Medicine, University Hospital Carl Gustav Carus,
Technical University Dresden, Deutschland. jkmed@rcs.urz.tu-dresden.de
AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it
might be helpful for the clinics involved if a longer time period
between the lymphoscintigraphy (LS) and surgery is possible. Therefore,
we investigated if a precise localization of the sentinel lymph node is
possible 24 hours after LS. METHODS: 78 patients with primary malignant
melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n =
34) were investigated. In 40 cases the tumor was localized on the trunk
and in 38 cases on the extremities. Mean MM thickness was 2.68 mm
(range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with
an average of 85 MBq of Tc-99m nanocolloid was performed one day prior
to surgery. Immediately after tracer application dynamic data
acquisition was started at a LFOV gamma camera followed by a whole body
scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours
after tracer administration the SLN was identified and the counts
registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from
which 86 could be resected. Nine MM showed two draining channels. After
24 hours 15.5% (as an average) of the initial counts could be measured
in the SLN. The uptake in the SLN in pre-operated versus patients with
primary tumor was statistically not significant (p = 0.4). In 16 cases
(20.5%) the SLN was tumor positive. Four of those patients developed
distant metastases and two died within the first year. None of the
patients with negative SLN developed distant metastases or died.
CONCLUSION: The remaining activity in the SLN up to 24 hours after
administration is sufficient for their intra operative localization. The
method of lymphoscintigraphy and localization of the SLN by a hand-held
gamma detector optimizes the intra operative identification of the SLN
in patients with malignant melanoma.
35
UI - 21433713
AU - Dummer R; Bosch U; Panizzon R; Bloch PH; Burg G; Task Force 'Skin
TI -
Cancer'. Swiss National Program against Cancer. Swiss Cancer League
Swiss guidelines for the treatment and follow-up of cutaneous melanoma.
SO - Dermatology 2001;203(1):75-80
AD - Department of Dermatology, University Hospital of Zurich, Switzerland.
dummer@derm.unizh.ch
Melanoma is the most common lethal cutaneous neoplasm. There is major
controversy over the best management of this malignancy. In order to
harmonize treatment and follow-up of melanoma patients, guidelines for
the management of melanoma in Switzerland have been inaugurated. They
have been approved by all Swiss medical societies involved in the care
of melanoma patients. Copyright 2001 S. Karger AG, Basel
36
UI - 21523850
AU - Serrano A; Tanzarella S; Lionello I; Mendez R; Traversari C;
TI -
Ruiz-Cabello F; Garrido F
Rexpression of HLA class I antigens and restoration of antigen-specific
CTL response in melanoma cells following 5-aza-2'-deoxycytidine
treatment.
SO - Int J Cancer 2001 Oct 15;94(2):243-51
AD - Servicio de Analisis Clinicos, Hospital Universitario Virgen de las
Nieves, Universidad de Granada, Granada, Spain.
Cell surface expression of HLA class I/peptide complexes on tumor cells
is a key step in the generation of T-cell-based immune responses.
Several genetic defects underlying the lack of HLA class I expression
have been characterized. Here we describe another molecular mechanism
that accounts for the complete absence of HLA class I molecule
expression in a tumor line (MSR3-mel) derived from a melanoma patient.
Hypermethylation of the MSR3-mel DNA, specifically of HLA-A and -B
genes, was identified, which resulted in loss of HLA class I heavy chain
transcription. Treatment of MSR3-mel cells with the demethylating agent
5'-aza-2'-deoxycytidine (DAC) allowed HLA-A and -B transcription,
restoring cell surface expression of HLA class I antigens and tumor cell
recognition by MAGE-specific cytotoxic T lymphocytes. The MSR3-mel line
was obtained from a metastatic lesion of a nonresponding patient
undergoing MAGE-3.A1 T-cell-based peptide immunotherapy. It is tempting
to speculate that the hypermethylation-induced lack of HLA class I
expression is the cause of the impaired response to vaccination. This
study provides the first evidence that DNA hypermethylation is used by
human neoplastic cells to switch off HLA class I genes, thus providing a
new route of escape from immune recognition. Copyright 2001 Wi
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