Originally published as JCO Early Release 10.1200/JCO.2008.21.3868 on April 13 2009

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Phase II Study of Tirapazamine, Cisplatin, and Etoposide and Concurrent Thoracic Radiotherapy for Limited-Stage Small-Cell Lung Cancer: SWOG 0222

From the Stanford University, Stanford; University of California, Davis Cancer Center, Sacramento, CA; Southwest Oncology Group Statistical Center, Seattle, WA; University of Kansas Medical Center, Kansas City; Wichita CCOP, Wichita, KS; and University of Colorado Denver, Aurora, CO.

Corresponding author: Quynh-Thu X. Le, MD, 875 Blake Wilbur Dr, MC 5847, Stanford, CA 94305-5847; e-mail: Qle{at}stanford.edu.

Purpose A SWOG pilot study (S0004) showed that tirapazamine (TPZ) when combined with concurrent chemoradiotherapy yielded a promising median survival of 22 months in limited-stage small-cell lung cancer (LSCLC). We report results of the phase II study designed to confirm this result.

Patients and Methods The concurrent phase consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. TPZ was given at 260 mg/m² on days 1, 29, and at 160 mg/m² on days 8, 10, 12, 36, 38, and 40. Consolidation consisted of two cycles of cisplatin and etoposide. Complete responders received prophylactic cranial irradiation. Results were considered promising if the median survival time was at least 21 months and of no further interest if 14 months.

Results S0222 was closed early due to a report of excess toxicity for TPZ in a head and neck cancer trial elsewhere. Of planned 85 patients, 69 were accrued. In 68 assessable patients, 17 (25%) had grade 3 to 4 esophagitis and eight (12%) had grade 3 febrile neutropenia during the concurrent phase. There were three possible treatment-related deaths, two in concurrent phase (one progressive disease not otherwise specified within 30 days, one pericardial effusion) and one in consolidation phase (esophageal hemorrhage). At a median follow-up of 35 months, median progression-free survival was 11 months (95% CI, 10 to 13 months) and median overall survival was 21 months (95% CI, 17 to 33 months).

Conclusion S0222 showed acceptable levels of toxicity and similar promising median survival as S0004. Further study of hypoxia-targeted therapy is warranted in LSCLC.

Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 31 to June 3, 2008.

Supported in part by the following PHS Cooperative Agreement Grants No. CA32102, CA38926, CA35431, CA35090, CA35261, CA45808, CA20319, CA67575, CA35281, CA22433, CA52654, CA12644, CA45368, CA46282, CA45560, CA35128, CA11083, CA37981, CA58658, CA76462, CA13612, CA42777, CA27057, CA14028, and CA118582 from the National Cancer Institute, Department of Health and Human Services.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: S0222.

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