Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma.

Abstract

Concurrent biochemotherapy for patients with advanced melanoma is capable of producing high CR and overall response rates and resulted in durable complete remissions in a small fraction of patients. Toxicity, although severe, was manageable in a routine inpatient hospital environment.

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%).…”

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

“…In this study, brain metastasis did not develop as the first or concurrent site of progressive disease in patients with either responsive disease (n ¼ 23) or with stable disease (n ¼ 13). Two prior published reports have indicated brain metastasis as a first site of progressive disease in four out of nine patients with a complete remission (Legha et al, 1998;O'Day et al, 1999). Moreover, in a retrospective case-controlled study of responders to DTIC or TMZ, it was found that responders to TMZ developed significantly less CNS relapses than responders to DTIC (Paul et al, 2002).…”

“…In previous studies of chemo-immunotherapy in metastatic melanoma, no response was observed in brain metastases despite objective tumour regression at extracranial sites (Legha et al, 1998;O'Day et al, 1999).…”

“…Recently, a combination of chemo-and immunotherapy has been investigated in several phase II studies (Khayat et al, 1993;Legha et al, 1998;O'Day et al, 1999;Richards et al, 1999) with responses of 40 -60%. However, in a recent phase III trial, survival did not improve with the addition of high-dose IL2 and IFNa to chemotherapy compared to chemotherapy alone (Rosenberg et al, 1999).…”

“…Its incidence is up to 75% in patients who die from metastatic melanoma (Amer et al, 1978). Brain metastases occur as the first site of progression in a significant proportion of patients with a CR, and in a large majority of patients with a PR following systemic treatment with DTIC or cisplatin as neither of these agents cross the blood -brain barrier (Legha et al, 1998;O'Day et al, 1999).…”