Tesetaxel, a new oral taxane, in combination with capecitabine: A phase I, dose-escalation study in patients with advanced solid tumors

Muhammad Wasif Saif, John Sarantopoulos, Amita Patnaik, Anthony W. Tolcher, Chris Takimoto, Murali Beeram

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: This phase I study was conducted primarily to determine the maximum tolerated dose (MTD) of tesetaxel, a novel, orally active, semisynthetic microtubule inhibitor of the taxane class, administered with oral capecitabine to patients with advanced solid tumors. Methods: During each 21-day cycle, patients were to receive tesetaxel on Day 1 and capecitabine twice daily on Days 1 through 14. The starting dose was tesetaxel 18 mg/m 2 and capecitabine 1,250 mg/m 2/day. These doses were increased based on tolerability during the first cycle according to the protocol-specified dose-escalation scheme. Response was evaluated every other treatment cycle according to RECIST. Serial blood samples were collected during the first and second cycles to explore possible pharmacokinetic drug interactions. Results: Twenty-seven patients were enrolled and treated. The most frequently reported dose-limiting toxicities were neutropenia and febrile neutropenia, with individual patients experiencing dose-limiting stomatitis and diarrhea. The MTD for the treatment regimen was defined as tesetaxel 27 mg/m 2 and capecitabine 2,500 mg/m 2/day. The most common ≥Grade 3 treatment-related adverse events included leukopenia (44% of patients) and neutropenia (41%). Of 22 evaluable patients, the best overall response was stable disease in 82% and progressive disease in 18%. No meaningful pharmacokinetic drug interactions were apparent. Conclusions: The results of this study demonstrate that these two orally active agents can be combined at the individual MTD of each drug with acceptable toxicity. These data further support the continued clinical development of tesetaxel both as a single agent and in combination with other active cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)1565-1573
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume68
Issue number6
DOIs
StatePublished - Dec 2011

Fingerprint

Tumors
Maximum Tolerated Dose
Drug interactions
Pharmacokinetics
Neoplasms
Toxicity
Neutropenia
Drug Interactions
Febrile Neutropenia
Stomatitis
Leukopenia
Therapeutics
Microtubules
Blood
Capecitabine
tesetaxel
taxane
Diarrhea
Pharmaceutical Preparations

Keywords

  • Advanced solid tumors
  • Capecitabine
  • Oral fluoropyrimidine
  • Oral taxane
  • Tesetaxel

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Tesetaxel, a new oral taxane, in combination with capecitabine : A phase I, dose-escalation study in patients with advanced solid tumors. / Saif, Muhammad Wasif; Sarantopoulos, John; Patnaik, Amita; Tolcher, Anthony W.; Takimoto, Chris; Beeram, Murali.

In: Cancer Chemotherapy and Pharmacology, Vol. 68, No. 6, 12.2011, p. 1565-1573.

Research output: Contribution to journalArticle

Saif, Muhammad Wasif ; Sarantopoulos, John ; Patnaik, Amita ; Tolcher, Anthony W. ; Takimoto, Chris ; Beeram, Murali. / Tesetaxel, a new oral taxane, in combination with capecitabine : A phase I, dose-escalation study in patients with advanced solid tumors. In: Cancer Chemotherapy and Pharmacology. 2011 ; Vol. 68, No. 6. pp. 1565-1573.
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