Efficacy and safety of pemetrexed in combination with cisplatin for malignant pleural mesothelioma: a phase I/II study in Japanese patients.
BACKGROUND
Pemetrexed in combination with cisplatin (Pem/Cis) is used globally for the treatment of malignant pleural mesothelioma (MPM). This Phase I/II study was conducted to determine the recommended dose (RD) (Phase I) of Pem/Cis, and evaluate the efficacy and safety (Phase II) in Japanese MPM patients.


METHODS
Key eligibility criteria were histologic diagnosis of MPM incurable by surgery, no prior chemotherapy, and a performance status 0-1. Under full vitamin supplementation, pemetrexed was intravenously administered on Day 1 of a 21-day cycle, followed by cisplatin. A cohort of six patients, starting from pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) (Level 1), were studied in the dose-escalation Phase I (Step 1). The RD determined in Step 1 was carried forward into Phase II (Step 2). Planned number of patients treated with Pem/Cis was 18-38.


RESULTS
In Step 1, 13 patients were enrolled: seven in Level 1 and six in Level -1 (pemetrexed 500 mg/m(2), cisplatin 60 mg/m(2)). Two of six evaluable patients had dose-limiting toxicities (pneumonitis and neutropenia) in Level 1, establishing Level 1 as the RD. In Step 2, 12 patients were enrolled, for a total of 19 patients treated at the RD. Seven patients achieved a partial response among these patients, for a response rate of 36.8% (95% confidence interval: 16.3-61.6); overall survival was 7.3 months. One drug-related death occurred due to worsening of a pre-existing pneumonia. Common grade 3/4 toxicities were neutropenia and decreased-hemoglobin.


CONCLUSIONS
The Pem/Cis combination provides promising activity and an acceptable safety profile for chemonaive Japanese MPM patients with the same recommend dosage and schedule used in rest of the world.
Nakagawa
Kazuhiko
K
Kinki University School of Medicine, Medical Oncology, 377-2 Ohnohigashi, Osakasayama 589-8511, Japan. nakagawa@med.kindai.ac.jp
Yamazaki
Koichi
K
Kunitoh
Hideo
H
Hida
Toyoaki
T
Gemba
Kenichi
K
Shinkai
Tetsu
T
Ichinose
Yukito
Y
Adachi
Susumu
S
Nambu
Yoshihiro
Y
Saijo
Nagahiro
N
Fukuoka
Masahiro
M
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012129:Respiratory Function Tests; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin