A phase I study of pemetrexed, carboplatin, and concurrent radiotherapy in patients with locally advanced or metastatic non-small cell lung or esophageal cancer.
OBJECTIVE
The primary objective of this phase I study was to determine the maximum tolerated dose for pemetrexed, alone and in combination with carboplatin, with concurrent radiotherapy.


METHODS
Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or esophageal cancer were treated every 21 days for two cycles. Regimen 1 was pemetrexed (200-600 mg/m(2)); regimen 2 was pemetrexed (500 mg/m(2)) with escalating carboplatin doses (AUC = 4-6). Both regimens included concurrent radiation (40-66 Gy; palliative-intent doses were lower).


RESULTS
Thirty patients (18 locally advanced and 12 metastatic with dominant local symptoms) were enrolled, with an Eastern Cooperative Oncology Group performance status of 0/1/2 (n = 8/21/1). All dose levels were tolerable for regimen 1 (n = 18: 15 NSCLC and 3 esophageal cancers) and regimen 2 (n = 12: all NSCLC). In regimen 1, one dose-limiting toxicity (grade 4 esophagitis/anorexia) occurred (500 mg/m(2)). Grade 3 neutropenia (3 of 18 patients) was the main hematologic toxicity. In regimen 2, one dose-limiting toxicity (grade 3 esophagitis) occurred (500 mg/m(2); AUC = 6); grade 3/4 leukopenia (4 of 12 patients) was the main hematologic toxicity. Four complete responses (2 pathology proven) and eight partial responses were observed. When systemically active chemotherapy doses were reached, further dose escalation was discontinued, and a phase II dose-range was established (pemetrexed 500 mg/m(2) and carboplatin AUC = 5-6).


CONCLUSIONS
The combination of pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5 or 6) with concurrent radiation is well tolerated, allows for the administration of systemically active chemotherapy doses, and shows signs of activity. To further determine efficacy, safety profile, and optimal dosing, the Cancer and Leukemia Group B study 30407 is currently evaluating this regimen in patients with unresectable stage III NSCLC.
Seiwert
Tanguy Y
TY
Section of Hematology/Oncology, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Connell
Philip P
PP
Mauer
Ann M
AM
Hoffman
Philip C
PC
George
Christopher M
CM
Szeto
Livia
L
Salgia
Ravi
R
Posther
Katherine E
KE
Nguyen
Binh
B
Haraf
Daniel J
DJ
Vokes
Everett E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000068437:Pemetrexed
D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin