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
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Leonard B Saltz
    735 Saltz
  2. Gary Schwartz
    384 Schwartz
  3. David H Ilson
    388 Ilson
  4. David R Spriggs
    325 Spriggs
  5. David P Kelsen
    511 Kelsen
  6. Nancy Kemeny
    512 Kemeny
  7. Deborah S Semple
    7 Semple