Phase I study of tirapazamine plus cisplatin/etoposide and concurrent thoracic radiotherapy in limited-stage small cell lung cancer (S0004): A southwest oncology group study

Quynh Thu Le, Jason McCoy, Stephen Williamson, Janice Ryu, Laurie E. Gaspar, Martin J. Edelman, Shaker R. Dakhil, Stanley D. Sides, John J. Crowley, David R Gandara

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the feasibility and a recommended phase II dose of tirapazamine when combined with chemoradiotherapy in limited-stage small cell lung cancer (LSCLC). Experimental Design: Concurrent chemoradiotherapy consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. Tirapazamine (260 mg/m2) was given 1 h before cisplatin with planned dose escalation to 330 mg/m2 in the absence of dose-limiting toxicity, defined as ≥33% esophagitis (grade 3 or above). Consolidation therapy consisted of two cycles of tirapazamine (330 mg/m2), cisplatin, and etoposide. Complete responders received prophylactic cranial irradiation. Results: Thirty patients were enrolled at the 260 mg/m2 tirapazamine dose. All had performance status of 0-1. By comparison with S9713, a predecessor Southwest Oncology Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3-4 esophagitis (34% versus 22%), vomiting (34% versus 23%), and febrile neutropenia (7% versus 2%). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44% and febrile neutropenia in 5% or patients. There were two treatment-related deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80%, and the median survival was 22 months. Conclusions: Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.

Original languageEnglish (US)
Pages (from-to)5418-5424
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number16
DOIs
StatePublished - Aug 15 2004

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tirapazamine
Small Cell Lung Carcinoma
Etoposide
Cisplatin
Radiotherapy
Thorax
Febrile Neutropenia
Chemoradiotherapy
Esophagitis
Neutropenia
Vomiting
Cranial Irradiation
Survival
Respiratory Tract Infections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase I study of tirapazamine plus cisplatin/etoposide and concurrent thoracic radiotherapy in limited-stage small cell lung cancer (S0004) : A southwest oncology group study. / Le, Quynh Thu; McCoy, Jason; Williamson, Stephen; Ryu, Janice; Gaspar, Laurie E.; Edelman, Martin J.; Dakhil, Shaker R.; Sides, Stanley D.; Crowley, John J.; Gandara, David R.

In: Clinical Cancer Research, Vol. 10, No. 16, 15.08.2004, p. 5418-5424.

Research output: Contribution to journalArticle

Le, Quynh Thu ; McCoy, Jason ; Williamson, Stephen ; Ryu, Janice ; Gaspar, Laurie E. ; Edelman, Martin J. ; Dakhil, Shaker R. ; Sides, Stanley D. ; Crowley, John J. ; Gandara, David R. / Phase I study of tirapazamine plus cisplatin/etoposide and concurrent thoracic radiotherapy in limited-stage small cell lung cancer (S0004) : A southwest oncology group study. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 16. pp. 5418-5424.
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abstract = "Purpose: To determine the feasibility and a recommended phase II dose of tirapazamine when combined with chemoradiotherapy in limited-stage small cell lung cancer (LSCLC). Experimental Design: Concurrent chemoradiotherapy consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. Tirapazamine (260 mg/m2) was given 1 h before cisplatin with planned dose escalation to 330 mg/m2 in the absence of dose-limiting toxicity, defined as ≥33{\%} esophagitis (grade 3 or above). Consolidation therapy consisted of two cycles of tirapazamine (330 mg/m2), cisplatin, and etoposide. Complete responders received prophylactic cranial irradiation. Results: Thirty patients were enrolled at the 260 mg/m2 tirapazamine dose. All had performance status of 0-1. By comparison with S9713, a predecessor Southwest Oncology Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3-4 esophagitis (34{\%} versus 22{\%}), vomiting (34{\%} versus 23{\%}), and febrile neutropenia (7{\%} versus 2{\%}). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44{\%} and febrile neutropenia in 5{\%} or patients. There were two treatment-related deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80{\%}, and the median survival was 22 months. Conclusions: Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.",
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T2 - A southwest oncology group study

AU - Le, Quynh Thu

AU - McCoy, Jason

AU - Williamson, Stephen

AU - Ryu, Janice

AU - Gaspar, Laurie E.

AU - Edelman, Martin J.

AU - Dakhil, Shaker R.

AU - Sides, Stanley D.

AU - Crowley, John J.

AU - Gandara, David R

PY - 2004/8/15

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N2 - Purpose: To determine the feasibility and a recommended phase II dose of tirapazamine when combined with chemoradiotherapy in limited-stage small cell lung cancer (LSCLC). Experimental Design: Concurrent chemoradiotherapy consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. Tirapazamine (260 mg/m2) was given 1 h before cisplatin with planned dose escalation to 330 mg/m2 in the absence of dose-limiting toxicity, defined as ≥33% esophagitis (grade 3 or above). Consolidation therapy consisted of two cycles of tirapazamine (330 mg/m2), cisplatin, and etoposide. Complete responders received prophylactic cranial irradiation. Results: Thirty patients were enrolled at the 260 mg/m2 tirapazamine dose. All had performance status of 0-1. By comparison with S9713, a predecessor Southwest Oncology Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3-4 esophagitis (34% versus 22%), vomiting (34% versus 23%), and febrile neutropenia (7% versus 2%). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44% and febrile neutropenia in 5% or patients. There were two treatment-related deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80%, and the median survival was 22 months. Conclusions: Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.

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