Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors Journal Article
| Authors: | Saltz, L. B.; Spriggs, D.; Schaaf, L. J.; Schwartz, G. K.; Ilson, D.; Kemeny, N.; Kanowitz, J.; Steger, C.; Eng, M.; Albanese, P.; Semple, D.; Hanover, C. K.; Elfring, G. L.; Miller, L. L.; Kelsen, D. |
| Article Title: | Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors |
| Abstract: | Purpose: In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction. Patients and Methods: to maximize the opportunity for synergy, we divided the cisplatin into four consecutive weekly treatments, followed by a 2-week rest. Each dose of cisplatin was immediately followed by a dose of irinotecan. The dose of cisplatin was fixed at 30 mg/m2/wk. The initial irinotecan dose was 50 mg/m2/wk and this was escalated by 30% increments in successive cohorts of three to six patients to establish the maximum-tolerated dose (MTD). Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed. Results: Of 35 patients with solid tumors enrolled onto this trial, 30 were assessable for toxicity and response. The MTD for this regimen was 30 mg/m2/wk of cisplatin plus 50 mg/m2/wk of irinotecan in previously treated patients and 30 mg/m2/wk of cisplatin plus 65 mg/m2/wk of irinotecan in chemotherapy-naive patients. Neutropenia was the dose-limiting toxicity (DLT) encountered in this trial. Diarrhea was infrequent and rarely dose-limiting. Seven of 30 assessable patients achieved a partial response. No alteration in irinotecan, SN-38, or SN-38G pharmacokinetics resulted from the administration of cisplatin with irinotecan. Conclusion: The administration of cisplatin and irinotecan on this weekly schedule provides a practical and well-tolerated regimen that has the potential to maximize any clinical synergy between the two agents. Evidence of substantial clinical activity was seen in this phase I study. |
| Keywords: | adult; clinical article; treatment outcome; aged; middle aged; clinical trial; drug tolerability; neutropenia; cisplatin; advanced cancer; cancer combination chemotherapy; diarrhea; solid tumor; neoplasms; antineoplastic combined chemotherapy protocols; drug administration schedule; 7 ethyl 10 hydroxycamptothecin; antineoplastic agents, phytogenic; camptothecin; drug resistance; irinotecan; drug synergism; drug response; phase 1 clinical trial; glucuronide; humans; human; male; female; priority journal; article; glucuronates |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 16 |
| Issue: | 12 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 1998-12-01 |
| Start Page: | 3858 |
| End Page: | 3865 |
| Language: | English |
| PUBMED: | 9850031 |
| PROVIDER: | scopus |
| DOI: | 10.1200/JCO.1998.16.12.3858 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work