Abstract
Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8–21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m2 bid, paclitaxel 60 mg/m2/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15–0.54), the median progression-free survival 5.5 months (95 % CI 2.8–10.8 months) and the median overall survival 10.8 months (95 % CI 6.0–32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity.
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Acknowledgments
We thank Dr. Christopher Roberts and Ms. Kathleen Sergott for providing detection reagents for immunohistochemistry for TP, TS, DPD. This trial has been registered at clinicaltrials.gov (registration identifer: NCT00201734). Registration Date: September 12, 2005.
Funding
Roche provided funding for the trial. The funding source did not influence the methodology, conduct of the trial, analysis or reporting of the results.
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Sameh Mikhail and Maryam B. Lustberg are primary authors with equal contribution.
Miguel Villalona-Calero and Tanios Bekaii-Saab are senior authors with equal contribution.
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Mikhail, S., Lustberg, M.B., Ruppert, A.S. et al. Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary. Cancer Chemother Pharmacol 76, 1005–1012 (2015). https://doi.org/10.1007/s00280-015-2877-6
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DOI: https://doi.org/10.1007/s00280-015-2877-6