Schedule dependent toxicity and efficacy of combined gemcitabine/paclitaxel treatment in mouse adenocarcinoma

A. Cividalli, F. Mauro, E. Livdi, F. Ceciarelli, P. Altavista, G. Cruciani, D. Tirindelli Danesi

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Abstract

Increased interest in combining drugs with different targets has emerged over recent years. Our study aims at evaluating the effectiveness of combined gemcitabine/paclitaxel treatment taking into consideration doses, schedules, and toxicity. A spontaneous mammary carcinoma was transplanted into the right-hind foot of C3D2F1 mice. Paclitaxel (in doses from 20 to 80 mg/kg b.w.) and gemcitabine (in doses from 30 to 480 mg/kg b.w.) were administered i.p. in single or fractionated treatments. Toxicity and tumor growth delay (TGD) were the endpoints. TGDs for different gemcitabine doses in single administration (120, 240, and 360 mg/kg) overlapped (TGD ≃ 2.5 days). Toxicity was very high in daily administration. Results with gemcitabine alone showed the efficacy of treatments every 3 days. TGDs in fractionated treatments of 60 and 120 mg/kg x 4 were of ≃ 16 days. Also in this case, tumor growth curves overlapped pointing out the uselessness of the high drug doses. For combined treatments, we used only fractionated protocols, administering gemcitabine every 3 days. Paclitaxel was administered alone in one or two fractions and with different sequences in respect to gemcitabine administration. With 120 mg/kg of gemcitabine all the protocols showed an increased unacceptable toxicity. The best result was obtained administering paclitaxel 40 mg/kg on days 1 and 15 and gemcitabine 60 mg/kg on days 3, 6, 9, and 12 (TGD = 38.2 days). The light toxicity and the high efficacy obtained with this protocol indicate the possible use of gemcitabine/paclitaxel treatment in clinical practice.
Original languageEnglish
Pages (from-to)461 - 467
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume126
Issue number8
DOIs
Publication statusPublished - 2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cividalli, A., Mauro, F., Livdi, E., Ceciarelli, F., Altavista, P., Cruciani, G., & Tirindelli Danesi, D. (2000). Schedule dependent toxicity and efficacy of combined gemcitabine/paclitaxel treatment in mouse adenocarcinoma. Journal of Cancer Research and Clinical Oncology, 126(8), 461 - 467. https://doi.org/10.1007/s004320050014