Feasibility study of docetaxel plus bevacizumab as first line therapy for elderly patients with advanced non-small-cell lung cancer: Thoracic Oncology Research Group (TORG) 1014.
BACKGROUND
Docetaxel monotherapy is one of the standard treatments for non-small-cell lung cancer in elderly patients. The addition of bevacizumab to docetaxel seems promising; however, the feasibility of this combination has not been investigated in such patients.


METHODS
Patients with advanced non-squamous non-small-cell lung cancer aged 70 years or older who had not previously received cytotoxic chemotherapy were enrolled. Patients in the Level 0 cohort received docetaxel 60 mg/m(2) and bevacizumab 15 mg/kg, whereas those in the Level-1 cohort received docetaxel 50 mg/m(2) and bevacizumab 15 mg/kg. Chemotherapy was repeated 3 weekly for six cycles. The primary endpoint was toxicity and the secondary endpoints were response rate, progression-free survival, overall survival, and proportion of patients who underwent three or more cycles of chemotherapy.


RESULTS
Twenty-one patients were enrolled from December 2010 to September 2012 at six institutes. Of the nine patients enrolled in Level 0, two experienced dose-limiting toxicity (febrile neutropenia and prolonged Grade 4 neutropenia in one patient, and Grade 3 infection in another patient) during the first cycle. Enrollment to the Level 0 cohort was terminated because two patients developed Grade 4 sepsis during later cycles. The remaining 12 patients were enrolled in the Level-1 cohort, in which two dose-limiting toxicities (prolonged Grade 4 neutropenia and Grade 3 increased aminotransferase level) were observed. No patient in the Level-1 cohort experienced Grade 4 nonhematologic toxicity. Grade 4 neutropenia occurred in 89 % of Level 0 patients and 50 % of Level-1 patients. The proportion of patients who experienced Grade 3/4 infection, febrile neutropenia or sepsis was 44 % in the Level 0 cohort, and 8 % in the Level-1 cohort. The overall response rate to chemotherapy and progression-free survival were 29 % (95 % CI, 11-52 %) and 5.9 months (95 % CI, 3.6-9.1 months), respectively. Efficacy outcomes did not differ significantly between the cohorts.


CONCLUSIONS
Toxicities were tolerable in level-1 cohort. The recommended dose of combination chemotherapy with docetaxel and bevacizumab for elderly patients was determined as 50 mg/m(2) of docetaxel and 15 mg/kg of bevacizumab and toxicities were tolerable. Further studies are warranted.


BACKGROUND
UMIN Clinical Trial Registry; UMIN000004240 .
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. ytakagi-tmd@umin.net.
Yusuke
Y
Takagi
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. yhosomi@cick.jp.
Yukio
Y
Hosomi
Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan. foshita@kcch.jp.
Fumihiro
F
Oshita
Yokohama Municipal Citizen's Hospital, 56 Kazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan. hi01-okamoto@city.yokohama.jp.
Hiroaki
H
Okamoto
Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan. nseki@med.teikyo-u.ac.jp.
Nobuhiko
N
Seki
Gunma Prefectural Cancer Center, 617-1 Takahayashi-Nishicho, Ota City, Gunma, 373-8550, Japan. kminato@gunma-cc.jp.
Koichi
K
Minato
Mitsui Memorial Hospital, 1 Kanda-Izumicho, Chiyoda-ku, Tokyo, 101-8643, Japan. hiaono@mitsuihosp.or.jp.
Hiromi
H
Aono
Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan. yamadak@kcch.jp.
Kouzo
K
Yamada
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. y-okuma@cick.jp.
Yusuke
Y
Okuma
Yokohama Municipal Citizen's Hospital, 56 Kazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan. na00-hida@city.yokohama.jp.
Naoya
N
Hida
Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan. takahiko0322@yahoo.co.jp.
Takahiko
T
Sakamoto
Gunma Prefectural Cancer Center, 617-1 Takahayashi-Nishicho, Ota City, Gunma, 373-8550, Japan. miura-y@gunma-cc.jp.
Yosuke
Y
Miura
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. myomota@cick.jp.
Makiko
M
Yomota
Yokohama Municipal Citizen's Hospital, 56 Kazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan. sato.akira.46v@st.kyoto-u.ac.jp.
Akira
A
Satoh
Mitsui Memorial Hospital, 1 Kanda-Izumicho, Chiyoda-ku, Tokyo, 101-8643, Japan. kunito_hideo@med.jrc.or.jp.|Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo, 150-8935, Japan. kunito_hideo@med.jrc.or.jp.
Hideo
H
Kunitoh
Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Sakyo-ku, Kyoto, 606-8501, Japan. smorita@kuhp.kyoto-u.ac.jp.
Kentaro
K
Sakamaki
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. mshibuya@cick.jp.
Masahiko
M
Shibuya
Yokohama Municipal Citizen's Hospital, 56 Kazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan. koshirow@pa3.so-net.ne.jp.
Koshiro
K
Watanabe
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008495:Medical Oncology; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab