Phase I dose escalation study of carboplatin to a fixed dose of irinotecan as first-line treatment of small cell lung cancer.
BACKGROUND
Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with small cell lung cancer.


METHODS
Patients with extensive small cell lung cancer received 50 mg/m(2) irinotecan on day 1, 8, and 15. Dose escalation of carboplatin on day 1 started in dose level 1 at an AUC of 5 mg x min/ml and was escalated to AUC 6 in level 2. Cycles were repeated on day 29. Dose escalation was evaluated after 3 consecutive patients. If no grade IV neutropenia lasting for > or =7 days or thrombopenia or non-hematologic toxicity > or = grade III occurred, treatment was continued in the next dose level.


RESULTS
16 patients were treated. DLT was reached in dose level 2 with 2 grade IV neutropenias and 1 grade IV thrombopenia and diarrhea. Toxicity was further investigated at dose level 1 in a total of 10 patients, which revealed 2 grade III neutropenias and 1 grade III diarrhea. Of 15 evaluable patients, 10 had a partial response, 3 had disease stabilization and 2 progressed.


CONCLUSIONS
Dose level 1 was found to be MTD, this dose is currently compared to the combination of etoposide plus carboplatin within a randomised phase II/III trial.
Schmittel
A
A
Medizinische Klinik III (Hämatologie, Onkologie and Transfusionsmedizin), Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany. scmittel@ukbf.fu-berlin.de
Schulze
K
K
Hütter
G
G
Krebs
P
P
Thiel
E
E
Keilholz
U
U
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects*; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011859:Radiography; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin