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Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx) in advanced solid cancers

Awada, A.a; Gil, T.a; Sales, F.a; Dubuisson, M.a; Vereecken, P.a; Klastersky, J.a; Moerman, C.a; de Valeriola, D.a; Piccart, M. J.a

doi: 10.1097/01.cad.0000127331.29310.8a

Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide exposure and subsequent depletion of O 6-alkylguanine alkyltransferase may improve the activity of temozolomide. The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity, their formulation and no significant overlapping toxicities. We conducted a study of a prolonged schedule of temozolomide (orally on days 1–7 and 15–21) plus Caelyx (day 1) every 28 days. Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to four dose levels (DL; temozolomide+Caelyx, mg/m2): DL1: 100+30 (n=3 patients), DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6 patients). Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC ≥7 days). Treatment delays and/or dose reductions (due to hematological toxicity) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide 125 mg/m2 (daily for 7 days every other week) plus Caelyx 40 mg/m2 (day 1 every 4 weeks). Other toxicities were mild. Antitumor activity was observed in eight patients, including one complete response (melanoma), three partial responses (one melanoma, two sarcomas) and four patients with stable disease (three melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions. This schedule of temozolomide allowed higher dose intensity (1750 mg/m2 in 4 weeks) compared to the standard 5-day regimen (1000 mg/m2 in the same amount of time).

aJules Bordet Institute, Brussels, Belgium

Correspondence to A. Awada, Jules Bordet Institute, Boulevard de Waterloo 121, 1000 Brussels, Belgium

Tel:+32 2 541 31 89; fax:+32 2 538 08 58;


Received 14 November 2003 Revised form accepted 26 February 2004

© 2004 Lippincott Williams & Wilkins, Inc.