Phase I/II trial of sequential chemoradiotherapy using a novel hypoxic cell radiosensitizer, doranidazole (PR-350), in patients with locally advanced non-small-cell lung Cancer (WJTOG-0002).

Abstract

PURPOSE:

This Phase I/II trial was conducted to assess the efficacy and safety of PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic radiation therapy (RT) after induction chemotherapy (CT) for locally advanced non-small-cell lung cancer (NSCLC).

METHODS AND MATERIALS:

Two cycles of cisplatin (80 mg/m(2)) and paclitaxel (180 mg/m(2)), or carboplatin (AUC = 6) and paclitaxel (200 mg/m(2)) were given before RT of 60 Gy in 30 fractions. In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m(2)) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses.

RESULTS:

In total, 37 patients were enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30 times. The major toxicity was radiation pneumonitis, with Grade 3 or more pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths. However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1 peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the median survival time (MST) and the 2-year survival rate were 15.9 months and 24%, respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2-year survival rate were 20.9 months and 33%, respectively.

CONCLUSIONS:

Thoracic RT combined with 30 daily administrations of PR-350 after induction CT was well tolerated and promising for locally advanced NSCLC.

• Authors: Yasumasa Nishimura, Kazuhiko Nakagawa, Koji Takeda, Masahiro Tanaka, Yoshihiko Segawa, Kayoko Tsujino, Shunichi Negoro, Nobukazu Fuwa, Toyoaki Hida, Masaaki Kawahara, Nobuyuki Katakami, Keiko Hirokawa, Nobuyuki Yamamoto, Masahiro Fukuoka, Yutaka Ariyoshi
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 69 Issue 3 Pg. 786-92 (Nov 01 2007) ISSN: 0360-3016 [Print] United States
• PMID: 17512126 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Imidazoles
• Radiation-Sensitizing Agents
• doranidazole
• Carboplatin
• Paclitaxel
• Cisplatin

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, radiotherapy)
• Cisplatin (administration & dosage)
• Combined Modality Therapy (methods)
• Female
• Humans
• Imidazoles (administration & dosage)
• Lung Neoplasms (drug therapy, radiotherapy)
• Male
• Middle Aged
• Paclitaxel (administration & dosage)
• Radiation Pneumonitis (etiology)
• Radiation-Sensitizing Agents (administration & dosage)
• Radiotherapy Dosage
• Survival Rate