Randomized phase II study comparing weekly docetaxel-cisplatin vs. gemcitabine-cisplatin in elderly or poor performance status patients with advanced non-small cell lung cancer.
BACKGROUND
Docetaxel/cisplatin (DP) and gemcitabine/cisplatin (GP) are standard treatment regimens for advanced non-small cell lung cancer (NSCLC). In spite of potent efficacy, the conventional 1-day DP is regarded as having more toxicity as compared with GP. There is increasing interest in a biweekly split administration of DP to reduce its toxicity. Hypothesis was that first-line biweekly DP is as safe as GP in the elderly or poor performance status (PS) patients.


METHODS
Chemotherapy-naïve patients with advanced NSCLC (IIIB/IV) who were elderly (65<) or PS (ECOG 2) were randomized to DP or GP arm by balancing for ECOG (0-1 vs. 2) and stage (IIIB vs. IV). DP comprised docetaxel (35 mg/m2)/cisplatin (30 mg/m2) iv on days 1 and 8, every 3 weeks. GP comprised gemcitabine (1000 mg/m2)/cisplatin (30 mg/m2) iv on days 1 and 8, every 3 weeks. Chemotherapy lasted up to 4-6 cycles or until progression. Primary endpoint was safety (proportion of grade 3/4 toxicities). Planned sample size was 49 patients in each arm.


RESULTS
From November 2009 to August 2012, a total of 99 patients were randomized (DP 50/GP 49) from nine institutions. Adenocarcinoma and squamous cell carcinoma were observed in 62% and 33% of patients, respectively. Toxicity profiles were comparable for both arms and the differences were not statistically significant except for anemia and leucocytopenia. Any grade of anemia (86 vs. 98%) and of leucocytopenia (18 vs. 43%) was more common in the GP arm with statistical significance. Oral mucositis tended to be predominant in the DP arm. Patients in the DP arm (51%) suffered grade 3 or higher toxicities as did 47% in the GP arm (47%). The most common grade 3 or higher toxicities were as follows: In the DP arm, neutropenia (8%), leucopenia (8%), anemia (4%), pneumonia with normal ANC (4%) and febrile neutropenia (2%) were observed. In the GP arm, anemia (15%), neutropenia (15%), pneumonia with normal ANC (4%), thrombocytopenia (4%) and leucopenia (2%) were observed. The best overall response rates (CR + PR) for the DP and GP arms were 20.0 and 21% with no CR, respectively, and disease control rates (CR + PR + SD) were 70.0 and 76%, respectively. Median progression-free survival and median overall survival were 3.7 and 14.9 months in the DP arm and 5.6 and 20.8 months in the GP arm, respectively.


CONCLUSIONS
This study showed that DP is similar to GP in terms of efficacy and toxicity in treatment of elderly or poor performance patients. Both regimens showed similar grade 3/4 toxicities with different profiles.
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
JoungSoon
J
Jang
Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Republic of Korea. miongsok@catholic.ac.kr.
Hoon-Kyo
HK
Kim
Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Byoung Chul
BC
Cho
Department of Internal Medicine, College of Medicine Yeungnam University, Daegu, Republic of Korea.
Kyung Hee
KH
Lee
Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Hwan-Jung
HJ
Yun
Department of Internal Medicine, Catholic University Yeouido St. Mary Hospital, Seoul, Republic of Korea.
In Sook
IS
Woo
Department of Internal Medicine, Dongsan Medical center, Keimyung University, Daegu, Republic of Korea.
Hong Suk
HS
Song
Department of Internal Medicine, Daegu Catholic University Medical Centre, Daegu, Republic of Korea.
Hun-Mo
HM
Ryoo
Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Republic of Korea.
Chi-Hong
CH
Kim
Department of Internal Medicine, Uijungbu St. Mary's Hospital, The Catholic Unviersity of Korea, Uijungbu, Republic of Korea.
Der-Sheng
DS
Sun
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
Jong Wook
JW
Shin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D002945:Cisplatin; D000093542:Gemcitabine
Cisplatin; Docetaxel; Elderly patients; Gemcitabine; Non-small cell lung cancer