Gynecologic Oncology. 2008 Mar;108(3):500-4. Epub 2008 Jan 11.
Tolerance and activity of oxaliplatin with protracted topotecan infusion in patients with previously treated ovarian cancer. A phase I study.
Hochster H, Chen TT, Lu JM, Hills D, Sorich J, Escalon J, Ivy P, Liebes L, Muggia F.
Division of Medical Oncology, New York University School of Medicine, NYU Cancer Institute, NY 10016, USA. howard.hochster@med.nyu.edu
Significance:
Ovarian cancer presents most often in advanced stages, and cisplatin or carboplatin are the most useful drugs for its treatment.
A third platinum drug, oxaliplatin, is not totally cross-resistant to the two above analogs, and we wanted to test whether it could be a useful treatment for recurrences.
Platinums followed by topotecan have enhanced anti-tumor effects but at a cost of enhanced toxicities; however, in this phase I trial oxaliplatin+topotecan was tolerated better than a prior combination with cisplatin, and several long-lasting improvements in disease status were documented --a phase II is ongoing.
Abstract:
BACKGROUND: Topotecan 14-day infusion combined with cisplatin was highly active in ovarian cancer, but too myelosuppressive. We therefore sought to evaluate the feasibility of substituting oxaliplatin for cisplatin to improve safety.
METHODS: Ovarian and primary peritoneal cancer patients, pretreated with at least one prior platinum-containing regimen, performance status (PS) 0-1, without prior pelvic radiation were eligible. Topotecan was continuously infused days 1-15; oxaliplatin was given days 1 and 15; cycles were repeated every 28 days. Five dose levels were explored: topotecan (mg/m2/day)/oxaliplatin (mg/m2) doses: (1) 0.2/65; (2) 0.2/75; (3) 0.2/85; (4) 0.3/85; (5) 0.4/85.
RESULTS: Twenty-three patients (20 ovarian, 1 tubal, and 2 peritoneal) were entered: median age 56 years (range, 37-77); PS: 0=12 and 1=11; histology: papillary serous 7, serous 4, adenocarcinoma 8, poorly differentiated 2. Median of 4 cycles were delivered. Grade 3 neutropenia occurred in 3 of 7 patients at level 5 (with fever at levels 4 and 5), without grade 4 neutropenia or thrombocytopenia. Other toxicities were mild and reversible (mainly gastrointestinal), except one grade 3 neuropathy and one oxaliplatin-related grade 3 hypersensitivity reaction. Six objective responses (five of them complete) were documented among 22 patients spanning several dose levels.
CONCLUSION: Topotecan continuous infusion, combined with oxaliplatin, was associated with no grade 4 hematologic toxicity and evidence of activity. The recommended phase II dose is topotecan 0.4 mg/m2/day continuous infusion d1-15 with oxaliplatin 85 mg/m2 on days 1 and 15. A phase II evaluation as second-line treatment for both platinum-sensitive and -resistant ovarian cancer recurrences is ongoing.
PMID: 18191187
