PMID- 22333598
OWN - NLM
STAT- MEDLINE
DCOM- 20120418
LR  - 20211203
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 106
IP  - 5
DP  - 2012 Feb 28
TI  - A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h 
      infusion in combination with carboplatin and etoposide in patients with 
      extensive-stage small cell lung cancer.
PG  - 839-45
LID - 10.1038/bjc.2012.21 [doi]
AB  - BACKGROUND: Bcl-2 family genes are frequently amplified in small cell lung cancer 
      (SCLC). A phase I trial was conducted to evaluate the safety of obatoclax, a 
      Bcl-2 family inhibitor, given in combination with standard chemotherapy. METHODS: 
      Eligible patients (3-6 per cohort) had extensive-stage SCLC, measurable disease, 
      </= 1 before therapy, Eastern Cooperative Oncology Group performance status 0 or 1, 
      and adequate organ function. Patients were treated with escalating doses of 
      obatoclax, either as a 3- or 24-h infusion, on days 1-3 of a 21-day cycle, in 
      combination with carboplatin (area under the curve 5, day 1 only) and etoposide 
      (100 mg m(-2), days 1-3). The primary endpoint was to determine the maximum 
      tolerated dose of obatoclax. RESULTS: Twenty-five patients (56% male; median age 
      66 years) were enrolled in three dose cohorts for each schedule. Maximum 
      tolerated dose was established with the 3-h infusion at 30 mg per day and was not 
      reached with the 24-h infusion. Compared with the 24-h cohorts, the 3-h cohorts 
      had higher incidence of central nervous system (CNS) adverse events (AEs); 
      dose-limiting toxicities were somnolence, euphoria, and disorientation. These CNS 
      AEs were transient, resolving shortly after the end of infusion, and without 
      sequelae. The response rate was 81% in the 3-h and 44% in the 24-h infusion 
      cohorts. CONCLUSION: Although associated with a higher incidence of transient CNS 
      AEs than the 24-h infusion, 3-h obatoclax infusion combined with 
      carboplatin-etoposide was generally well tolerated at doses of 30 mg per day. 
      Though patient numbers were small, there was a suggestion of improved efficacy in 
      the 3-h infusion group. Obatoclax 30 mg infused intravenously over 3 h on 3 
      consecutive days will be utilised in future SCLC studies.
FAU - Chiappori, A A
AU  - Chiappori AA
AD  - H. Lee Moffitt Cancer Center and Research Institute, Thoracic Oncology Program, 
      12902 Magnolia Drive, Tampa, FL 33612, USA. Alberto.Chiappori@moffitt.org
FAU - Schreeder, M T
AU  - Schreeder MT
FAU - Moezi, M M
AU  - Moezi MM
FAU - Stephenson, J J
AU  - Stephenson JJ
FAU - Blakely, J
AU  - Blakely J
FAU - Salgia, R
AU  - Salgia R
FAU - Chu, Q S
AU  - Chu QS
FAU - Ross, H J
AU  - Ross HJ
FAU - Subramaniam, D S
AU  - Subramaniam DS
FAU - Schnyder, J
AU  - Schnyder J
FAU - Berger, M S
AU  - Berger MS
LA  - eng
GR  - P30 CA076292/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120214
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Indoles)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Pyrroles)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - BG3F62OND5 (Carboplatin)
RN  - QN4128B52A (obatoclax)
SB  - IM
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/*administration & dosage/adverse effects
MH  - Central Nervous System/drug effects
MH  - Drug Administration Schedule
MH  - Etoposide/*administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Indoles
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors
MH  - Pyrroles/*administration & dosage/adverse effects
MH  - Small Cell Lung Carcinoma/*drug therapy/pathology
PMC - PMC3305978
EDAT- 2012/02/16 06:00
MHDA- 2012/04/19 06:00
PMCR- 2013/02/28
CRDT- 2012/02/16 06:00
PHST- 2012/02/16 06:00 [entrez]
PHST- 2012/02/16 06:00 [pubmed]
PHST- 2012/04/19 06:00 [medline]
PHST- 2013/02/28 00:00 [pmc-release]
AID - bjc201221 [pii]
AID - 10.1038/bjc.2012.21 [doi]
PST - ppublish
SO  - Br J Cancer. 2012 Feb 28;106(5):839-45. doi: 10.1038/bjc.2012.21. Epub 2012 Feb 
      14.