Alternating temozolomide and low doses rIL-2 in patients with metastatic melanoma. An open non-randomized phase I/II study

Abstract

7541 Background: Temozolomide (Temodal) is a novel chemotherapeutic agent that is rapidly absorbed, it offers 100% bioavailability as an oral preparation and achieves significant CNS penetration. It has been shown that combination rIL-2 in high doses and DTIC in melanoma gave higher response rate than the single agents alone. Temozolomide in sequence with low doses IL-2 might be an efficacious treatment where a cytostatic drug and a cytokine, which activates the immune system, may synergistically eliminate the tumour with low cumulative toxicity. Methods: The primary objective of this study was to determine the safety and tolerance of Temozolomide 200 mg/m2 orally once dayly from day 1 to 5, in sequential combination with subcutaneous injection of 4.5 × 106 IU rIL-2 (Proleukin™) at days 8–11, 15–18 and 22–25 in patients with measurable progressive metastatic malignant melanoma without radiological signs of CNS metastases. The secondary objectives were to determine tumour response and time to progression (TTP). Results: Forty-seven patients were recruited and 27 were included of which 4 were non-evaluable for response. Twenty-three patients tolerated the regimen with side effects below grade 3 according to WHO . Two patients suspended the treatment because of side effects above WHO grade 3 already during the first course with Temozolomide. Seven patients showed no tumour progression during the first four treatment cycles. These, consequently, continued to receive the combined treatment and to be monitored, until signs of relapse or max 21 courses. Two patients had CR, 3 PR and 2 SD. Six of twenty-five treated patients (24%) developed brain metastases during follow up. Conclusions: Temozolomide in combination with rIL-2 is a well tolerated regimen for out-patient treatment. Responders have long TTP, possibly due to rIL-2 treatment. No significant financial relationships to disclose.