Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma.

Abstract

Sixty-four patients with histologically confirmed metastatic malignant melanoma were entered on a prospectively controlled randomized trial. Patients received dacarbazine (DTIC) alone or DTIC plus interferon (IFN) alfa-2b. Patients were reasonably balanced with respect to age, sex, performance status (PS), site of metastases, and number of metastatic sites. Objective response (complete plus partial remission [CR + PR]) was documented in six patients on DTIC and in 16 patients on DTIC plus IFN alfa-2b. Median time to treatment failure (TTF) and median survival are significantly better on the combination arm, with some long-term CRs observed. More toxicity was encountered in the combination arm, which was acceptable except in three patients where treatment was discontinued because of IFN toxicity.

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

“…Severe fatigue and flu-like symptoms together with breathlessness were also more common in those treated with IL-2 + IFN-a in addition to chemotherapy, although none of these other differences were statistically significant. (1998) 77(8) (Falkson et al, 1991), although this was not confirmed subsequently in two larger randomized trials (Thomson et al, 1993;Bajetta et al, 1994). Interleukin 2 (IL-2) enhances the cellular immune response by stimulating natural killer cells and specific cytotoxic T-cell expansion.…”

“…There have been several trials of combined chemoimmunotherapy in an attempt to improve response rates and the duration of responses by using potential additive or synergistic interactions. Early reports of the addition of IFN-a to DTIC suggested improved response rates and diseasefree survivals, although this was not borne out by subsequent randomized trials (Falkson et al, 1991;Thomson et al, 1993;Bajetta et al, 1994). The addition of IL-2 to chemotherapy has been disappointing in reported phase II trials with response rates of 24-41% (Flaherty et al, 1993).…”

“…The dose of IL-2 used was based on experience of the immunological changes that occur with IL-2 given subcutaneously, using a schedule that was previously well tolerated (Atzpodien et al, 1993;Castello et al, 1993). Similarly, the dose of interferon has been used in a number of interferon-DTIC studies (Falkson et al, 1991).…”

Malignant mucosal melanoma of the head and neck — a review

“…33 In small, randomised trials that compared the dacarbazine alone and with a combined with either tamoxifen or IFN-α 2. The latter two produced higher response rate than dacarbazine alone, 14,16 but phase III ECOG trial failed to prove it. 17 Chemotherapeutic agents in various combination have been used in the treatment of stage IV patients.…”

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon α for metastatic melanoma: a multicentre phase II study

“…Several chemoimmunotherapy schedules have been clinically tested. The results of DTIC plus IFN-ax are conflicting, with most trials failing to show a benefit of the combination over DTIC alone (Falkson et al, 1991;Thompson et al, 1993;Bajetta et al, 1994;Mulder et al, 1994;Received 29 November 1996 Revised 20 January 1997 Accepted 29 January 1997 Correspondence to: CJA Punt, Department of Medical Oncology University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands Falkson et al, 1996). Phase II results of DTIC plus IL-2 did not suggest a clear benefit for this combination (Stoter et al, 1991;Fiedler et al, 1992).…”