Skin Cancer & Melanoma

FREEPORT, NY-In a phase III clinical trial of 30 patients with xeroderma pigmentosum, use of a topically applied DNA repair enzyme (T4N5 liposome lotion) for 1 year reduced the incidence of basal cell carcinoma by 30% and actinic keratoses by 68%, compared with placebo.

VENICE, Italy-Adjuvant therapy with the investigational vaccine Melacine helps prevent relapses in patients with stage IIA melanoma, investigators from the Southwest Oncology Group (SWOG) 9035 Study Group announced at the Fifth World Conference on Melanoma. Mela-cine, being developed by Corixa (Seattle), consists of a mixture of allogeneic melanoma cell lysates plus an immunologic adjuvant (Detox).

NEW YORK-An antisense drug that targets a protein that interferes with the actions of chemotherapeutic agents is entering phase III trials, said Raymond P. Warrell, Jr., MD, president and chief executive officer, Genta Inc., Berkeley Heights, New Jersey.

NEW YORK-For some stage IV melanoma patients who achieve only a partial response or stable disease on a regimen of biochemotherapy, a maintenance strategy using interleukin-2 (IL-2) may prolong survival and in some instances produce durable complete responses, California researchers have discovered. Steven J. O’Day, MD, associate director, medical oncology, John Wayne Cancer Institute at St. John’s Health Center, Santa Monica, reported the encouraging results of a pilot study of the biotherapy maintenance strategy at the Chemotherapy Foundation Symposium XVIII.

Sentinel lymph node biopsy has rapidly evolved into the standard of care for node-negative melanoma. It has been used at the Roswell Park Cancer Institute (RPCI) since 1993, and through periodic reviews of results, several modifications have been

BETHESDA, Md-The FDA’s Oncologic Drugs Advisory Committee (ODAC) declined in a unanimous vote to recommend that the agency approve histamine hydrochloride injections (Maxim Pharmaceuticals) for adjuvant use with interleukin-2 (IL-2) in the treatment of adult patients with advanced melanoma that has metastasized to the liver.

Although melanoma is a relatively chemoresistant malignancy, systemic chemotherapy remains the primary treatment for metastatic melanoma. The observation of vasculogenic mimicry in aggressive melanoma has

HAMBURG, Germany-Attempts to improve on interferon-based regimens for melanoma with alternative immuno-stimulant strategies are proving less successful than originally hoped, according to presentations at the 25th Congress of the European Society of Medical Oncology (ESMO).

SEATTLE-Melanoma patients with specific human leukocyte antigen (HLA) phenotypes may respond better to an investigational therapeutic vaccine known as Melacine than those without the phenotype, Vernon Sondak, MD, reported for the Southwest Oncology Group (SWOG) at the Society of Biological Therapy annual meeting.

Temozolomide, an oral alkylating agent, has shown activity against metastatic melanoma. The drug is schedule dependent and is given daily for 5 days. Altering the schedule may enhance its activity by depletion of the protein O6-alkylguanine-DNA

NEW ORLEANS-Management of some patients with melanoma of the lower extremity could potentially stop with sentinel lymph node (SLN) biopsy, according to results presented at the 68th Annual Scientific Meeting of the American Society of Plastic and Reconstructive Surgeons. The study suggests that regional micrometastases of melanoma in the lower extremity are likely confined to the sentinel lymph nodes harvested by lymphadenectomy in some patients, said Lee L.Q. Pu, MD, PhD, resident in plastic surgery, University of South Florida, Tampa.

In the left image, a collar-button shaped choroidal melanoma is seen at lower right. Note the wrinkles in the macular retina caused by tumor growth. At right, after palladium-103 plaque radiation therapy, the choroidal melanoma appears darker and smaller as evidenced by resolution of the macular retinal folds. These photographs of this rare ocular cancer are from the extensive collection of NYU ophthalmologist Paul T. Finger, MD. More ocular images can be seen on the Eye Cancer

PITTSBURGH-An immunomod-ulating agent, histamine dihydrochloride (Maxamine), used in combination with interleukin-2 (IL-2) may improve survival in certain patients with stage IV malignant melanoma.

The SIAscope uses light and sophisticated computer software to construct an image of each part of the skin. The technique shows when a mole is invading deeper into the skin than normal, allowing early diagnosis of malignant melanoma. The SIAscope, based on spectrophotometric intracutaneous analysis (SIA), was researched at Birmingham University and developed by Cambridge-based Astron Clinica. It is in clinical trials at various sites in the United Kingdom. Dr. Marc Moncrieff (pictured, left) is one of the doctors conducting the trials.

NEW ORLEANS-A prospective study in colorectal cancer patients has found that sentinel lymph node (SLN) mapping correctly predicts the presence or absence of nodal metastases, with a very low incidence of skip metastases (disease in a non-SLN), as it does in melanoma and breast cancer.

NEW ORLEANS-Long-term follow-up of patients who underwent surgical excision of intermediate-thickness melanomas offers valuable information regarding the risk of local recurrence, especially as it relates to treatment.

Avax Technologies, Inc., has released 9-year follow-up data of stage III melanoma patients from company-sponsored phase II studies of M-Vax, an individualized cell-based vaccine for cancer. Ernest W. Yankee, PhD, the company’s executive vice-president, presented the data at the 26th annual meeting of the Clinical Oncological Society of Australia in Melbourne.

MANCHESTER, UK-Oral temo-zolomide (Temodar) is as effective as intravenous dacarbazine (DTIC) in advanced metastatic malignant melanoma and is a reasonable alternative for many patients, according to a phase III trial. Temozolomide

WASHINGTON-Insufficient evidence exists to support or reject the inclusion of routine skin cancer screenings in Medicare coverage, according to a new report by the Institute of Medicine (IOM). A second IOM report urges the Health Care Financing Administration (HCFA) to end uncertainties about whether it will cover routine care for patients taking part in clinical trials by stating that it will.

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).