A recent study1 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.
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
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.
. http://jco.ascopubs.org/content/early/2014/10/14/JCO.2013.53.1590/suppl/DC3. Accessed November 13, 2014.