Adjuvant Interferon, Follow-up Key Issues In Melanoma: NCCN

FORT LAUDERDALE, Fla--Once primary melanoma is excised, choosing amongadjuvant treatment options is a difficult decision, Daniel G. Coit, MD,of Memorial Sloan-Kettering Cancer Center, said at the National ComprehensiveCancer Network (NCCN) annual meeting. Dr. Coit presented the network'spreliminary guidelines for melanoma, along with John A. Thompson, MD, ofthe University of Washington, Seattle.

Adjuvant treatment and the schedule and intensity of follow-up werethe areas that generated the most discussion among the melanoma guidelinespanel members, Dr. Coit said.

Dr. Thompson noted that "interferon alfa-2b (Intron A) is the firstadjuvant treatment in melanoma that has induced a statistically significantimprovement in relapse-free and overall survival."

In considering guidelines for adjuvant treatment, Dr. Thompson saidthat the NCCN panel focused on "patients who can be rendered surgicallyfree of disease, but who retain a very high risk of relapse in the nextfive years."

For patients with melanomas less than 4 mm thick, the recommendationis surgery alone. Patients with melanomas greater than 4 mm thick or anyonewith positive lymph nodes regardless of thickness should be consideredfor interferon alfa therapy or a clinical trial, Dr. Thompson said.

For patients who are sentinel node positive, Dr. Thompson said thatthe preliminary NCCN recommendation is generally to proceed with lymphnode dissection. "At that point, if no evidence of residual metastaticdisease exists, the clinician may proceed with adjuvant systemic therapywith interferon," he said.

Dr. Coit called detection of recurrence the cornerstone of the follow-upof the cancer patient. He emphasized that the NCCN guidelines for follow-up"are, for the most part, arbitrary, that is, they are points of departure."

Follow-up for Early Melanoma

For early melanoma (stages I and II), the committee adhered to the NCIconsensus guideline, Dr. Coit said, which recommends history and physicaland skin examination every six months for two years, then annually. Optionalfollow-up recommendations include chest x-ray, and LDH every 6 to 12 months.He added that, for more advanced disease, "there really are very littledata to suggest what we should do."

Patients with thicker melanomas and those with node-positive melanomasrecur earlier than those with node-negative or thinner melanomas, he noted."In node-positive melanomas, about 80% of all recurrences will beseen within the first two years, and by five years, well over 95% of allrecurrences will be seen," he said.

Although recurrence is less common in the node-negative and thin melanomagroup, the risk of recurrence is spread out over a much longer period oftime. "Only about 50% of recurrences are seen by two years, and thatcurve stretches out to 10 and 20 years," Dr. Coit said.

The NCCN recommends more intensive frequency of follow-up in patientswith positive nodes or thick primary melanomas, with yearly follow-up afterthe fifth year, "looking both at the risk of second primary melanoma,a lifelong event, and the likelihood of a late recurring melanoma,"Dr. Coit said.

Optional recommendations for follow-up in these patients are chest x-rayand laboratory studies, including LDH, alkaline-phosphatase, and completeblood cell count, every 6 to 12 months, and abdominal/pelvic/chest CT scan,especially if interferon alfa is being considered, he added.

Dr. Coit emphasized that the NCCN guidelines to date are a "work-in-progress"and will be followed by ongoing review and refinement within the NCCN memberinstitutions.

Primary Treatment

Dr. Coit cautioned that melanoma is primarily a disease of younger people,and it is crucial that its management in the early phases be determined."We're in the midst of a melanoma epidemic," he said, "andit's becoming a public health problem, ranking second only to adult leukemiain terms of years of potential life lost."

For patients with in situ melanomas, the NCCN preliminary recommendationsfor primary treatment include wide excision with a 0.5 cm margin; for thosewith melanomas less than 1 mm thick, a 1 cm margin; and for those withmelanomas measuring between 1 and 4 mm, or greater than 1 mm thick, a wideexcision with a 2 cm margin.

In patients who present with stage III melanoma, wide excision of theprimary melanoma with a regional lymph node dissection is appropriate,and results in a long-term cure rate of approximately 30% of patients,Dr. Coit said.

For more advanced regional disease, there are many options, he said.Those included in the preliminary NCCN practice guidelines are surgicalexcision; intradermal injection of nonspecific immunotherapy agents, likeBCG (bacillus Calmette-Guérin), DNCB (dinitrochlor-obenzene), orinterferon-alfa; hyperther-mic perfusion with melphalan (Alkeran); enrollmentin a clinical trial; or systemic therapy.

For patients with systemic metastases not amenable to surgical resection,Dr. Coit said, the recommended treatment is systemic chemotherapy withdacarbazine (DTIC), platinum-based combination therapy, or investigationaltherapy on a clinical trial.

NCCN Melanoma Guidelines Panel

Alan Houghton, MD
Chair, Memorial Sloan-Kettering
Cancer Center

Daniel Coit, MD
Co-chair, Memorial Sloan-Kettering
Cancer Center

William Bloomer, MD
The Radiation Medicine Institute,
Evanston Hospital

Antonio Buzaid, MD
M.D. Anderson Cancer Center

David Chu, MD
The City of Hope National Medical Center

Burton Eisenberg, MD
Fox Chase Cancer Center

Joan Guitart, MD
Northwestern University

Timothy Johnson, MD
University of Michigan

Stanley Miller, MD
The Johns Hopkins Oncology Center

Steven Sener, MD
Evanston Hospital

Kenneth Tanabe, MD
Massachusetts General Hospital

John Thompson, MD
University of Washington

Marshall Uriat, MD
University of Alabama at Birmingham

Mike Walker, MD
Ohio State University