Phase I Dose Escalation Study With Irinotecan, Capecitabine, Epirubicin, and Granulocyte Colony-Stimulating Factor Support for Patients With Solid Malignancies

Becerra, Carlos; Verma, Udit; Tran, Hia T.; Tavana, Denise; Williams, Noelle S.

doi:10.1097/coc.0b013e31815a438f

Cited by 2 publications

(2 citation statements)

References 18 publications

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“…Besides hematological disturbances several other effects, including diarrhea, hand-foot syndrome, hypotension, abdominal pain, and asthenia have been reported [19]. Therefore, in the light of the research performed so far, blood toxicity seems to be a major side effect of CAP.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells

Wiśniewska-Jarosińska

Śliwiński

Kasznicki

et al. 2010

Mol Biol Rep

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The interaction between a chemical and a cell may strongly depend on whether this cell is normal or pathological. Side effects of anticancer drugs may sometimes overcome their benefit action, so it is important to investigate their effect in both the target and normal cells. Capecitabine (Xeloda, CAP), a prodrug of 5-fluorouracil, is mainly used in colon cancer, but little is known about its action in head and neck cancer. We compared the cyto- and genotoxicity of CAP in head and neck HTB-43 cells and normal human lymphocytes by comet assay and flow cytometry. CAP at concentration up to 50 μM significantly decreased the viability of the cancer cells, whereas it did not affect normal lymphocytes. The drug did not interact with isolated plasmid DNA, but it damaged DNA in both cancer and normal cells. However, the extent of the damage in the former was much higher than in the latter. CAP induced apoptosis in the cancer cells, but not in normal lymphocytes. Pre-treatment of the cells with the nitrone spin traps α-(4-pyridil-1-oxide)-N-tert-butylnitrone and N-tert-butyl-α-phenylnitrone decreased the extent of CAP induced DNA damage, suggesting that free radicals may be involved in the formation of DNA lesions induced by CAP. The drug evoked an increase in the G0/G1 cell population accompanied by a decrease in the S cell population. CAP may evoke a pronounced cyto- and genotoxic effects in head and neck cancer cells, whereas it may or may not induce such effects in normal cells to far lesser extent.

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Section: Introductionmentioning

confidence: 99%

Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells

Wiśniewska-Jarosińska

Śliwiński

Kasznicki

et al. 2010

Mol Biol Rep

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“…These SSBs lead to formation of double strand breaks during DNA synthesis and subsequent apoptosis. CAMP was evaluated in phase I [23] and phase II [24] clinical trials for breast cancer but was found to be too toxic for further use. Irinotecan is approved for use in colon cancer and in phase II clinical trials has shown activity against metastatic breast cancer [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Synergistic interactions between aminoflavone, paclitaxel and camptothecin in human breast cancer cells

Reinicke

Kuffel

Goetz

et al. 2009

Cancer Chemother Pharmacol

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Purpose Aminoflavone is a unique DNA damaging agent currently undergoing phase I evaluation in a prodrug form (AFP464). In anticipation of combination regimens, interactions between aminoflavone and several anticancer drugs were investigated in MCF-7 breast cancer cells to determine whether synergistic cancer cell killing effects were observed. Methods Colony formation assays were performed to assess the effect of combining aminoflavone with a variety of anticancer drugs. Changes in initial uptake, retention or efflux of aminoflavone and the second agent were compared to the behavior of drugs alone. Key features required for aminoflavone activity in cell culture models were also explored, focusing on the obligatory induction of CYP1A1/1A2 and binding of reactive aminoflavone metabolites to tumor cell total macromolecules and DNA. Results Aminoflavone was synergistic when co-incubated with paclitaxel, camptothecin or SN38. Uptake of neither aminoflavone nor any of the other three compounds was altered in combination incubations. Paclitaxel did not inhibit DNA binding of aminoflavone metabolites, while camptothecin did. Aminoflavone-induced CYP1A1 induction was observed in the presence of camptothecin or paclitaxel. Conclusions Aminoflavone is a promising therapeutic agent for breast cancer due to its unique mechanism of action compared to commonly used drugs. Combined treatments utilizing aminoflavone in conjunction with paclitaxel or camptothecin may provide an even greater cytotoxic effect than achieved with aminoflavone alone.

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Phase I Dose Escalation Study With Irinotecan, Capecitabine, Epirubicin, and Granulocyte Colony-Stimulating Factor Support for Patients With Solid Malignancies

Abstract: The recommended doses for phase II studies: irinotecan 180 mg/m2 day 1, epirubicin 50 mg/m2 day 2, and capecitabine 750 mg/m2 twice daily days 2 to 7 of each 21-day cycle. This combination is reasonably active and warrants evaluation in the phase II setting.

Cited by 2 publications

References 18 publications

Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells

Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells

Synergistic interactions between aminoflavone, paclitaxel and camptothecin in human breast cancer cells

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