175 mg m _ 2 on day 1 2.9

Overall response rate



second-line treatment for ovarian cancer show it to be well tolerated, although the objective response rate of ~ 15% in four studies was assessed as 'modest but definite.'44 In combination with cisplatin as a first-line treatment, overall response rates (ORRs) of 70% have been reported in two studies.45 The gemcitabine/carboplatin combination was approved for the treatment of ovarian cancer in Europe in July 2004 following a phase III study of 356 patients previously treated with platinum-based therapy. The gemcitabine/carboplatin study group showed an increased median time to progression of 8.6 months versus 5.8 months for patients treated with carboplatin alone, and ORRof 47% in the treatment group versus 31% in the carboplatin control group.46 The triplet combination of gemcitabine/carboplatin/ paclitaxel as a first-line therapy has shown even greater efficacy, and the ORR was determined to be 89.7-100%, with 35 of 53 patients having complete remission.47 In bladder cancer, gemcitabine monotherapy is effective with ORR ranging from 36% to 45%,48'49 as are doublet combinations gemcitabine with cisplatin, paclitaxel, or docetaxel (ORR 60%, 40%, and 33%, respectively).50-52 Clofarabine

Clofarabine (12) was given accelerated approval in late December 2004 for use in pediatric acute lymphoblastic leukemia (ALL), based on induction of complete responses in 6 of 49 patients, and 9 additional partial responses or complete responses without platelet recovery. Clinical studies demonstrating increased survival or other clinical benefit have not been conducted. The synthesis of clofarabine reported in 199253 stemmed from attempts to modify the structure of fludarabine (18) and cladribine (10) and retain desirable cytotoxic effects while avoiding neurotoxicities associated with fludarabine. Cladribine replaces the 2-fluoro substituent with chlorine, and clofarabine additionally replaces the 2'-hydroxyl with fluorine.

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