A Phase i Study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer

Balazs Halmos, Yuxia Jia, Joseph A. Bokar, Pingfu Fu, David J. Adelstein, Rosalyn Juergens, Mary Beth Rodal, Afshin Dowlati

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer. Methods This was a Phase I study (NCT00732745) with a standard 3 + 3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy. Results Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on day 1, docetaxel at 35 mg/m2 on days 1 and 8 and vandetanib 100 mg PO daily of 21-day treatment cycles. As dose limiting toxicity (DLT) was reached in 2 out of 3 patients in cohort 1 (one grade 3 and one grade 4 diarrhea with dehydration), 6 patients were treated then at dose level -1 (O 80 mg/m2 on day 1, D 30 mg/m2 on days 1 and 8, V 100 mg PO daily days 1-21) in which no further DLTs were observed. This dose was established as maximum tolerated dose and is the recommended phase 2 dose. 8 out of 9 enrolled patients had adenocarcinoma. At dose level 1, 1 of the 3 patients had a documented partial response and 2 patients had stable disease. At dose level -1, 1 of 6 patients achieved a complete response, 2 of 6 patients had stable disease, and 3 of 6 patients had progressive disease. Conclusions Vandetanib added to oxaliplatin and docetaxel showed manageable toxicity and limited activity in advanced GE cancer.

Original languageEnglish (US)
Pages (from-to)1244-1250
Number of pages7
JournalInvestigational New Drugs
Volume31
Issue number5
DOIs
StatePublished - Oct 2013
Externally publishedYes

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oxaliplatin
docetaxel
Neoplasms
Therapeutics
Maximum Tolerated Dose
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Dehydration

Keywords

  • Docetaxel
  • Gastroesophageal cancer
  • Oxaliplatin
  • Phase I
  • Vandetanib

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

A Phase i Study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer. / Halmos, Balazs; Jia, Yuxia; Bokar, Joseph A.; Fu, Pingfu; Adelstein, David J.; Juergens, Rosalyn; Rodal, Mary Beth; Dowlati, Afshin.

In: Investigational New Drugs, Vol. 31, No. 5, 10.2013, p. 1244-1250.

Research output: Contribution to journalArticle

Halmos, Balazs ; Jia, Yuxia ; Bokar, Joseph A. ; Fu, Pingfu ; Adelstein, David J. ; Juergens, Rosalyn ; Rodal, Mary Beth ; Dowlati, Afshin. / A Phase i Study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer. In: Investigational New Drugs. 2013 ; Vol. 31, No. 5. pp. 1244-1250.
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T1 - A Phase i Study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer

AU - Halmos, Balazs

AU - Jia, Yuxia

AU - Bokar, Joseph A.

AU - Fu, Pingfu

AU - Adelstein, David J.

AU - Juergens, Rosalyn

AU - Rodal, Mary Beth

AU - Dowlati, Afshin

PY - 2013/10

Y1 - 2013/10

N2 - Introduction This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer. Methods This was a Phase I study (NCT00732745) with a standard 3 + 3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy. Results Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on day 1, docetaxel at 35 mg/m2 on days 1 and 8 and vandetanib 100 mg PO daily of 21-day treatment cycles. As dose limiting toxicity (DLT) was reached in 2 out of 3 patients in cohort 1 (one grade 3 and one grade 4 diarrhea with dehydration), 6 patients were treated then at dose level -1 (O 80 mg/m2 on day 1, D 30 mg/m2 on days 1 and 8, V 100 mg PO daily days 1-21) in which no further DLTs were observed. This dose was established as maximum tolerated dose and is the recommended phase 2 dose. 8 out of 9 enrolled patients had adenocarcinoma. At dose level 1, 1 of the 3 patients had a documented partial response and 2 patients had stable disease. At dose level -1, 1 of 6 patients achieved a complete response, 2 of 6 patients had stable disease, and 3 of 6 patients had progressive disease. Conclusions Vandetanib added to oxaliplatin and docetaxel showed manageable toxicity and limited activity in advanced GE cancer.

AB - Introduction This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer. Methods This was a Phase I study (NCT00732745) with a standard 3 + 3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy. Results Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on day 1, docetaxel at 35 mg/m2 on days 1 and 8 and vandetanib 100 mg PO daily of 21-day treatment cycles. As dose limiting toxicity (DLT) was reached in 2 out of 3 patients in cohort 1 (one grade 3 and one grade 4 diarrhea with dehydration), 6 patients were treated then at dose level -1 (O 80 mg/m2 on day 1, D 30 mg/m2 on days 1 and 8, V 100 mg PO daily days 1-21) in which no further DLTs were observed. This dose was established as maximum tolerated dose and is the recommended phase 2 dose. 8 out of 9 enrolled patients had adenocarcinoma. At dose level 1, 1 of the 3 patients had a documented partial response and 2 patients had stable disease. At dose level -1, 1 of 6 patients achieved a complete response, 2 of 6 patients had stable disease, and 3 of 6 patients had progressive disease. Conclusions Vandetanib added to oxaliplatin and docetaxel showed manageable toxicity and limited activity in advanced GE cancer.

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KW - Phase I

KW - Vandetanib

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