Phase I study of tirapazamine and cisplatin in patients with recurrent cervical cancer Journal Article
| Authors: | Aghajanian, C.; Brown, C.; O'Flaherty, C.; Fleischauer, A.; Curtin, J.; Roemeling, R. V.; Spriggs, D. R. |
| Article Title: | Phase I study of tirapazamine and cisplatin in patients with recurrent cervical cancer |
| Abstract: | Objectives. Tirapazamine (SR 4233) is a benzotriazine compound exhibiting substantial differential toxicity for hypoxic cells. A large enhancement in tumor cell killing has been demonstrated in preclinical studies when tirapazamine was combined with cisplatin. This phase I study was undertaken to establish a safe dose combination of tirapazamine and cisplatin when administered to patients with recurrent cervical carcinoma. Methods. Tirapazamine was administered as an intravenous infusion over 2 hr, followed 1 hr later by cisplatin intravenously over 1 hr, every 21 days. All patients received prophylactic antiemetics consisting of ondansetron, dexamethasone, and lorazepam. The planned dose escalation levels of tirapazamine were 195, 260, 330, and 390 mg/m2. The cisplatin dose was fixed at 75 mg/m2. Results. A total of 12 patients were treated with 43 courses of therapy. Patients were heavily pretreated. Eleven of the 12 had prior radiotherapy and 5 of the 12 had prior cisplatin-based chemotherapy. A maximally tolerated dose of 330 mg/m2 was defined for this patient population. The dose-limiting toxicity was nausea and vomiting. All 12 patients were also evaluated for response. Two major responses were seen (17%). In addition, there were three minor responses (25%) and 4 patients achieved disease stabilization (33%). All major and minor responses were seen at the highest dose level tested of 330 mg/m2. Conclusions. Tirapazamine and cisplatin is an interesting drug combination in the treatment of cervical cancer. Phase II testing is planned. |
| Keywords: | adult; clinical article; aged; middle aged; clinical trial; fatigue; cisplatin; cancer combination chemotherapy; diarrhea; dose response; recurrent cancer; neoplasm recurrence, local; anemia; leukopenia; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; lorazepam; dexamethasone; uterine cervix cancer; ondansetron; phase 1 clinical trial; tumor growth; uterine cervical neoplasms; cell killing; intravenous drug administration; tirapazamine; growth inhibition; dna strand; triazines; humans; human; female; priority journal; article |
| Journal Title: | Gynecologic Oncology |
| Volume: | 67 |
| Issue: | 2 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1997-11-01 |
| Start Page: | 127 |
| End Page: | 130 |
| Language: | English |
| DOI: | 10.1006/gyno.1997.4841 |
| PUBMED: | 9367694 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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167Brown -
112Curtin -
613Aghajanian -
325Spriggs -
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