A recent study found that biochemotherapy may provide better relapse-free survival (RFS) than high-dose interferon (HDI) in patients with high-risk melanoma, but according to an expert the regimen is unlikely to gain wide clinical use.
The standard HDI regimen for malignant melanoma lasts a year. This study was designed to determine whether biochemotherapy can provide similar benefits with a shorter duration of treatment.
The research team, led by Lawrence E. Flaherty, MD, of Wayne State University in Detroit, Michigan, recruited 402 patients with stage IIIA-N2a through IIIC-N3 melanoma.
Patients were randomly assigned to receive high-dose interferon alfa-2b in a 1-year regimen or biochemotherapy consisting of cisplatin, vinblastine, dacarbazine, interleukin-2, and low-dose interferon alfa-2b given in a 12-day cycle, repeated every 3 weeks for a total of 3 cycles. Patients were hospitalized for the first 5 days of each treatment cycle.
A total of 88 patients (43%) completed the 1-year HDI regimen and 159 (80%) completed the 9-week biochemotherapy regimen. In the HDI arm, 55 patients (27%) discontinued treatment for relapse and 39 (19%) for adverse events, whereas in the biochemotherapy arm 2 patients (1%) discontinued for relapse and 29 patients (15%) for adverse events.
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Median follow-up was 7.2 years. Grade 3 or higher toxicity occurred in 64% of patients treated with HDI and 76% of patients treated with biochemotherapy. The rate of grade 4 toxicity was sharply higher in the biochemotherapy arm: 40% compared with 7%.
Median RFS was significantly better among patients treated with biochemotherapy (4.0 years vs. 1.9 years; HR 0.75; 95% confidence interval [CI] 0.58, 0.97; P = 0.029). Five-year RFS was 48% in the biochemotherapy arm (95% CI 41%, 55%) and 39% in the HDI arm (95% CI 32%, 46%).
Demographic analysis showed that female patients who had 1 to 3 positive nodes, satellite/in-transit metastases with nodal involvement, or macroscopic nodal presentation had significantly better RFS with biochemotherapy than with HDI.
Despite the improvements in RFS, biochemotherapy was not associated with a benefit in overall survival (OS). Median OS was 6.7 years among patients receiving HDI patients and 9.9 years among patients receiving biochemotherapy (HR 0.98; 95% CI 0.74, 1.31; P = 0.55). The 5-year OS was 56% (95% CI 49%, 63%) in both groups.
Commenting on the study, Jeffrey S. Weber, MD, of Moffitt Cancer Center in Tampa, Florida, who was not a member of the research team, said, “While these results are encouraging, and provide some evidence that clinical benefit in the form of prolonged relapse-free survival may be provided by a moderately toxic biochemotherapy regimen, the lack of survival advantage and the side effect profile as well as the in-patient nature of the biochemotherapy regimen are major disadvantages that will mitigate against its adoption in clinical practice.”2
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Noting that new drugs for malignant melanoma have become available since the year this trial was designed (1999), Dr. Weber said, “The cost-benefit quotient and the promise of newer, less toxic outpatient drugs make it unlikely that biochemotherapy will get much use in the future as adjuvant treatment for high-risk melanoma.”
“Have new developments passed these results by?” Dr. Weber asked. “I would say yes.”
- Flaherty LE, Othus M, Atkins MB, et al. Southwest Oncology Group S0008: A phase III trial of high-dose interferon alfa-2b versus cisplatin, vinblastine, and dacarbazine DTIC, plus interleukin-2 and interferon in patients with high-risk melanoma—an Intergroup Study of Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. J Clin Oncol. 2014. [Epub ahead of print.] DOI: 10.1200/JCO.2013.53.1590.
- Weber JS. Biochemotherapy: As time goes by? J Clin Oncol. [podcast]. http://jco.ascopubs.org/content/early/2014/10/14/JCO.2013.53.1590/suppl/DC3. Accessed November 13, 2014.