A phase 2 clinical trial of panitumumab monotherapy in Japanese patients with metastatic colorectal cancer.
OBJECTIVE
Panitumumab, a fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR), has antitumor activity and an acceptable safety profile in patients with metastatic colorectal cancer (mCRC). This Phase 2 study evaluated efficacy, pharmacokinetics and safety of panitumumab in Japanese patients with mCRC who developed progressive disease during or after fluoropyrimidine, irinotecan and oxaliplatin chemotherapy.


METHODS
Eligible patients had histologically proven colorectal adenocarcinoma and EGFR tumor expression in > or =1% of tumor cells by immunohistochemistry. Patients received panitumumab 6 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) by independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), pharmacokinetic parameters and incidence of adverse events.


RESULTS
Fifty-two patients received at least one dose of panitumumab. Seven patients had partial responses for a confirmed ORR of 13.5% (95% CI: 5.6, 25.8). Median PFS was 8.0 weeks (95% CI: 7.4, 11.4) and median OS was 9.3 months (95% CI: 7.1, 12.8). Panitumumab pharmacokinetics were consistent with prior studies in Japanese and non-Japanese patients. The most common treatment-related adverse events (all, worst grade 3) were acne (81%, 2%), dry skin (62%, 0%), rash (46%, 2%), paronychia (33%, 2%), pruritus (33%, 0%) and hypomagnesemia (33%, 0%). No adverse event of infusion reaction was reported by the investigators.


CONCLUSIONS
Panitumumab monotherapy was active in Japanese patients with chemotherapy-refractory mCRC, with pharmacokinetic and safety profiles similar to those seen in prior studies.
Muro
Kei
K
Aichi Cancer Center Hospital, Nagoya, Aichi, Japan. kmuro@aichi-cc.jp
Yoshino
Takayuki
T
Doi
Toshihiko
T
Shirao
Kuniaki
K
Takiuchi
Hiroya
H
Hamamoto
Yasuo
Y
Watanabe
Hiroyuki
H
Yang
Bing-Bing
BB
Asahi
Daisuke
D
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D007564:Japan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D011743:Pyrimidines / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D011743:Pyrimidines; D000077150:Oxaliplatin; D000077544:Panitumumab; D000077146:Irinotecan; D066246:ErbB Receptors; D002166:Camptothecin