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A phase I trial of topotecan and gemcitabine administered weekly for 3 consecutive weeks to patients with advanced tumors
Author(s) -
Sun Weijing,
Stevenson James P.,
Gallagher Maryann,
Giantonio Bruce,
Algazy Kenneth,
Haller Dan,
Vaughn David,
Raskay Barbara J.,
O'Dwyer Peter J.
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010715)92:2<414::aid-cncr1337>3.0.co;2-w
Subject(s) - topotecan , gemcitabine , medicine , gastroenterology , oncology , pharmacology , chemotherapy , pancreatic cancer , combination therapy , cancer
Abstract BACKGROUND The complementary action of gemcitabine and topotecan on DNA metabolism suggested the potential for their use in combination chemotherapy. Gemcitabine, a synthetic cytidine analogue chain terminator, and topotecan, a topoisomerase‐1 inhibitor, have been reported to have broad antitumor activity and are approved for clinical use. METHODS The cytotoxicity of the combination in various models in vitro was additive. In the current study, the authors conducted a Phase I study to determine the recommended Phase II doses and toxicity profile of gemcitabine and topotecan when administered weekly in combination. Gemcitabine (400–1000 mg/m 2 ) was given intravenously over 30 minutes followed by a 15‐minute infusion of topotecan (0.75–2.5 mg/m 2 ) weekly for 3 consecutive weeks in a 4‐week treatment cycle. Thirty‐eight patients with advanced refractory solid tumors and good performance status were treated. RESULTS Myelosuppression in the form of granulocytopenia and thrombocytopenia were the major dose‐limiting toxicities. Other toxic effects included anemia, nausea, and elevated hepatic transaminases. Partial responses were observed in two patients (one with nonsmall cell lung carcinoma and one with pancreatic carcinoma). Disease stabilization occurred in five patients (three with pancreatic carcinoma, one with rectal carcinoma, and one with metastatic carcinoma of an unknown primary site). Gemcitabine, 1000 mg/m 2 , and topotecan, 2.5 mg/m 2 , were the maximum tolerated doses for this combination. CONCLUSIONS The results of the current study showed that the combination of weekly gemcitabine and topotecan for 3 weeks in a 4‐week cycle schedule appeared to be well tolerated and was associated with clinical activity. Therefore, this combination is recommended for a further Phase II evaluation. Cancer 2001;92:414–9. © 2001 American Cancer Society.