Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-α

Abstract

The sequential combination of CVD with IL-2 + IFN-alpha appears to have produced an increase in the number of durable responses in patients with metastatic melanoma. The toxicity of this program, although severe, was manageable. The biochemotherapy regimen produced an apparent increase in the median survival compared to that observed with the CVD regimen. However, a prospective comparison of these two regimens will be required to confirm these observations.

Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-α) and interleukin (IL-2) in patients with metastatic melanoma

“…These toxicities are well recognized in patients receiving IL-2 and IFN-a therapy. However, in contrast to the studies of high-dose intravenous IL-2 and subcutaneous IFN-a with chemotherapy (Richards et al, 1992;Legha et al, 1993;Legha et al, 1996), the severity and incidence of these toxicities was lower in our study.…”

“…In a similar biochemotherapy programme, Richards et al (1992) In our randomized trial, we chose the BCDT regimen as the standard chemotherapy regimen, based on the phase II data available at the time, which suggested this to be the most active regimen (DelPrete et al, 1994). In view of the severe toxicities experienced by the addition of intravenous IL-2 to chemotherapy (Richards et al, 1992;Legha et al, 1993;Legha et al, 1996), we elected for a subcutaneous delivery for IL-2. The reduced toxicity and improved tolerability of low-dose subcutaneous IL-2 is well documented (Castello et al, 1993) and has been shown previously to induce clear changes in immunological parameters with a significant rise in NK cells (Azpodien et al, 1993 (Demchak et al, 1991).…”

“…Our study was set up befoXre the results of the recent randomized study reporting a superior response rate for chemotherapy followed by biotherapy (Legha et al, 1996 (Rusthoven et al, 1996). Very few CRs were reported in that trial (< 5%), and none were detected in our chemotherapy-alone group.…”

Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM)

“…We observed an overall objective response in 34.3% of patients treated with the combined chemoimmunotherapy which is comparable with earlier trials achieving response rates between 23% to 64% (Atkins et al, 1994;Atzpodien et al, 1995;Feun et al, 1995;Hoffmann et al, 1998;Johnston et al, 1998;Legha, 1998;Middleton et al, 2000;Pyrhonen et al, 1992;Rosenberg et al, 1999;Thompson et al, 1997). Whereas in previous clinical trials, introducing cytokines in chemotherapeutic regimens yielded an enhanced efficacy (Atkins et al, 1994;Legha et al, 1996), our results raise doubts concerning the potential benefits of the presently used dosages of IL-2 and INF-a for therapy of metastatic melanoma since objective response rates of patients treated with chemotherapy alone were similar (29.9%) to sequential chemoimmunotherapy (34.3%).…”

“…While primarily in phase II studies several authors claimed a clear advantage of this chemoimmunotherapy over chemotherapy alone (Legha et al, 1996;Richards et al, 1992), more recently randomized trials raised doubts about the effectiveness and benefit of this combination (Johnston et al, 1998;Rosenberg et al, 1999).…”