Biochemotherapy for the treatment of metastatic malignant melanoma: a systematic review.
BACKGROUND
The incidence of malignant melanoma has increased in recent years. Current therapies for metastatic melanoma include chemotherapy and a variety of immunotherapeutic choices. With no established standard treatment option, the evaluation of biochemotherapy is warranted.


METHODS
A systematic review of the literature was conducted to locate randomized controlled trials, meta-analyses, systematic reviews, and evidence-based practice guidelines published up to April 2007.


RESULTS
Nine eligible randomized controlled trials were identified, including six comparing chemotherapy alone to biochemotherapy (chemotherapy combined with interleukin-2 and interferon). Response rates were significantly higher with biochemotherapy in only two trials, although when data were pooled, biochemotherapy was superior to chemotherapy on response (relative risk, 1.52; 95% confidence interval, 1.24-1.87; p<0.0001) but did not delay time to progression (Hazard ratio, 0.80; 95% confidence interval, 0.63-1.01; p=0.06). Biochemotherapy was not associated with a statistically significant survival benefit in any of the individual trials or in a pooled analysis (Hazard ratio, 0.95; 95% confidence interval, 0.78-1.17; p=0.64). Biochemotherapy is a toxic therapy, and patients are likely to experience serious hematologic, gastrointestinal, cutaneous, and constitutional toxicities, although when conducted in the correct setting, grade 3 and 4 effects appear to be manageable, and treatment-related death can be minimized.


CONCLUSIONS
The results of available studies are inconsistent with regard to benefit (response, time-to-progression, and survival) and show consistently high toxicity rates. Therefore, biochemotherapy is not recommended for the treatment of metastatic malignant melanoma in adults.
Hamm
Caroline
C
Windsor Regional Hospital, 2220 Kildare Road, Windsor, Canada N8W 2X3. caroline_hamm@wrh.on.ca
Verma
Shailendra
S
Petrella
Teresa
T
Bak
Kate
K
Charette
Manya
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008545:Melanoma; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000188:drug therapy*; D015996:Survival Rate
D007376:Interleukin-2