Skin Cancer & Melanoma

SILVER SPRING, Md-With some uncommonly strong and negative comments to Food and Drug Administration staff, the Oncologic Drugs Advisory Committee (ODAC) refused to recommend approval of Roferon-A (interferon alfa-2a recombinant, Hoffmann-La Roche) for use as an adjuvant treatment of surgically resected malignant melanoma without clinical evidence of nodal disease.

IOWA CITY, Iowa-A surprising new study shows that some melanoma cells can form themselves into vascular channels and provide a tumor’s blood supply without the need for angiogenesis (the growth of new blood vessels from existing blood vessels). The resulting channels, which are lined by melanoma cells and basement membrane (see Figure 1), function as a vascular system for the tumor without the endo-thelium-lined blood vessels produced through angiogenesis.

Haigh et al provide thoughtful, detailed summary of 3 decades of intensive work aimed at developing active, specific immuno-therapies (vaccines) for patients with melanoma. However, as the 20th century draws to a close, the key question is: Can any vaccine be considered an effective therapy for patients with melanoma? To rephrase the question: What constitutes proof of efficacy for a melanoma vaccine, and have any vaccines met those criteria? In a word, the answer to the first question is “no.” The answer to the second question, however, requires more elaboration.

In organizing this brief, but informative review of human melanoma vaccines, Haigh et al have provided an important service to the readers of oncology and are to be commended for their efforts. Their descriptions of the variety of vaccine technologies currently under development and their assessment of the strengths and weakness of each are, for the most part, fair and conservative.

Investigation into the therapeutic use of vaccines in patients with metastatic melanoma is critically important because of the lack of effective conventional modalities. The most extensively studied melanoma vaccines in clinical trials are whole-cell preparations or cell lysates that contain multiple antigens capable of stimulating an immune response. Unfortunately, in the majority of studies, immune responses to these vaccines have not translated into a survival advantage. Advances in tumor cell immunology have led to the identification of candidate tumor cell antigens that can stimulate an immune response; this, in turn, has allowed for refinements in vaccine design. However, the exact tumor antigens that should be targeted with a specific vaccine are unknown. The univalent antigen vaccines, which have greater purity, ease of manufacturing, and reproducibility compared with polyvalent vaccines, may suffer from poorer efficacy due to immunoselection and appearance of antigen-negative clones within the tumor. Novel approaches to vaccine design using gene transfection with cytokines and dendritic cells are all promising. However, the induction of immune responses does not necessarily confer a therapeutic benefit. Therefore, these elegant newer strategies need to be studied in carefully designed clinical trials so that outcomes can be compared objectively with standard therapy. If survival is improved with these vaccine approaches, their ease of administration and lack of toxicity will firmly entrench active specific vaccine immunotherapy as a standard modality in the treatment of the melanoma patient.[ONCOLOGY 13(11):1561-1574, 1999].

PHILADELPHIA-The autologous, dinitrophenyl (DNP)-modified vaccine M-Vax has previously been shown to produce a 5-year overall survival rate of 58% in melanoma patients with large, resectable metastases in one regional nodal site.

PHILADELPHIA-Injections of vaccinia virus genetically engineered to deliver the GM-CSF gene proved safe and led to regression of dermal lesions in patients with stage IV melanoma, said Michael J. Mastrangelo, MD, professor of medicine, Thomas Jefferson University, Jefferson Medical College.

ATLANTA-Researchers at the Karmanos Cancer Institute/Wayne State University, Detroit, and the Cytokine Working Group report encouraging response rates and acceptable toxicity using an outpatient regimen for metastatic malignant melanoma. The phase II trial combined cisplatin (Platinol) and DTIC chemotherapy with interleukin-2 (IL-2) and interferon-alfa biotherapy.

NEW YORK-The first clinical trials of a live genetically engineered Salmonella typhimurium bacterium are expected to get underway in the second half of this year in patients with cutaneous metastases of melanoma and breast cancer.

A pharmaceutical treatment may offer patients an alternative to the usual surgical removal of basal cell carcinomas, according to a presentation at the annual meeting of the American Academy of Dermatology in New Orleans.

ORLANDO-Sentinel lymph node biopsy, which is widely used to detect micrometastases in melanoma and in breast cancer, can also identify colorectal cancer patients who have metastatic disease and should have adjuvant chemotherapy, Sukamal Saha, MD, reported in a plenary presentation at the Society of Surgical Oncology’s 52nd Annual Cancer Symposium (see Figure).

NEW YORK-Actinic keratoses should be treated or removed, according to the consensus of the American Academy of Dermatology, American Cancer Society, and Skin Cancer Foundation. “It is not merely a cosmetic issue,” said Jeffrey Callen, MD, chief of the Division of Dermatology, University of Louisville. Because of their potential to develop into skin cancer, these lesions should be regarded as a serious health problem, he said at a media briefing sponsored by the Academy as part of its Melanoma/Skin Cancer Detection and Prevention Month.

NEW YORK-The association between intermittent but intense sun exposure and malignant melanoma has long been recognized, though the reasons behind it have not been understood. Researchers have now uncovered mechanisms likely to explain why this specific pattern of sun exposure leads to the deadliest form of skin cancer.

NEW YORK-The American Academy of Dermatology has unveiled three new public service advertising campaigns targeting a broad audience with the message that prevention and early detection are the best weapons against skin cancer.

BETHESDA, Md-The Oncology Drugs Advisory Committee (ODAC) has voted not to recommend that the FDA approve Temodal (temozolomide, Schering) for the first-line treatment of patients with metastatic malignant melanoma. The 10 to 0 vote, with one member abstaining, followed a spirited discussion in which committee members not only questioned the value of Temodal in advanced melanoma, but also that of DTIC-Dome (dacarbazine, Bayer), which the FDA approved in 1975 for treating the disease.

WASHINGTON-Medicare will cover three additional uses of positron emission tomography (PET) for the diagnosis and treatment of cancer. In addition to the previously covered uses for the diagnostic evaluation of solitary pulmonary nodules and for staging non-small-cell lung cancer, PET will now be covered for the detection and localization of recurrent colorectal cancer with rising CEA levels; the staging and characterization of both Hodgkin’s and non-Hodgkin’s lymphoma in place of a gallium scan or lymphangiogram; and the identification of metastases in melanoma recurrence in place of gallium scans.

Dr. Natale Cascinelli, president of the World Health Organization (WHO) Melanoma Program, declared intraoperative lymphatic mapping to be the standard of care for melanoma. He made this statement during his presentation of the abstract, “An Overview on Sentinel Lymph Node Dissection” at the 9th International Congress on Anti-Cancer Treatments in Paris.

The promise of using reverse transcriptase–polymerase chain reaction (RT-PCR) technology for the detection of circulating prostate cancer cells in peripheral blood, although technically feasible at the molecular level, has proven clinically impractical for routine implementation in patient management. Reverse transcriptase–polymerase chain reaction has been successfully applied to detect and quantify (relatively speaking) genes that are differentially expressed in cells and tissues obtained from patients during various stages of malignant growth. In addition, the method has been applied to the detection of circulating cancer cells in peripheral blood using highly specific primer sets for specific molecular targets. These include epithelial cell cytokeratins for breast cancer, as well as enzymes, such as tyrosinase for melanoma and prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) for prostate cancer, using either nonnested or nested methodologies.

ATHENS-High-dose interferon-alfa-2b (Intron A, IFN) is the only regimen shown to improve relapse-free survival in high-risk melanoma and should be considered a reference standard for adjuvant therapy in this disease, John Kirkwood, MD, of the University of Pittsburgh, said in a debate at this year’s European Society for Medical Oncology (ESMO) Congress.

Over the past decade, knowledge of the way in which the immune system can be used to fight cancer has greatly increased.

TORONTO--Swiss researchers have shown that positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) detects metastases more accurately than conventional imaging techniques in patients with malignant melanoma and increases the cost of staging by only 1.7%

TORONTO--Patients with high-risk melanoma may benefit from use of whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for primary staging, researchers from the University of Frankfurt/Main reported at the 45th Annual Meeting of the Society of Nuclear Medicine.

Sunscreen can help reduce the risk of malignant melanoma, contrary to the finding of a study that received considerable media

LOS ANGELES--A modified M.D. Anderson biochemotherapy regimen for metastatic melanoma that includes interleukin-2 (IL-2) has antitumor activity and is suitable for testing in a cooperative group setting, according to analysis of pilot trial data. The pilot study precedes the larger phase III ECOG/SWOG 3695 intergroup trial that will compare the regimen to CVD (cisplatin, vinblastine, and dacarbazine).

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested

NEW ORLEANS--Increasing levels of melanoma-inhibiting activity (MIA) protein indicate increasing disease activity in melanoma patients, according to research presented at the American Association for Cancer Research meeting.

BUFFALO, NY--Early studies comparing the combination of chemotherapy and immunotherapy with traditional chemotherapy alone suggest that the combination may improve immune responses in patients with metastatic melanoma, said Thomas Olencki, DO, Department of Hematology/Medical Oncology, Cleveland Clinic Foundation.

In the next 5 to 10 years, we may have the answer to the question of whether vaccines can fulfill their promise to become an effective treatment for melanoma, predict Brian J. Czerniecki, md, PhD, and Isabelle Bedrosian, md, in the latest issue of The Melanoma Letter, a publication of The Skin Cancer Foundation. These researchers are experimenting with a new kind of vaccine to combat disseminated melanoma.