Phase II study of tirapazamine, cisplatin, and etoposide and concurrent thoracic radiotherapy for limited-stage small-cell lung cancer: SWOG 0222.
OBJECTIVE
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.


METHODS
The concurrent phase consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. TPZ was given at 260 mg/m(2) on days 1, 29, and at 160 mg/m(2) 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 < or = 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).


CONCLUSIONS
S0222 showed acceptable levels of toxicity and similar promising median survival as S0004. Further study of hypoxia-targeted therapy is warranted in LSCLC.
Stanford University, Stanford, CA, USA. Qle@stanford.edu
Quynh-Thu X
QT
Le
James
J
Moon
Mary
M
Redman
Stephen K
SK
Williamson
Primo N
PN
Lara
Zelanna
Z
Goldberg
Laurie E
LE
Gaspar
John J
JJ
Crowley
Dennis F
DF
Moore
David R
DR
Gandara
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004941:Esophagitis / Q000139:chemically induced; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D055752:Small Cell Lung Carcinoma / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D015996:Survival Rate; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage* / Q000633:toxicity
D000970:Antineoplastic Agents; D014227:Triazines; D000077704:Tirapazamine; D005047:Etoposide; D002945:Cisplatin