PMID- 21140147
OWN - NLM
STAT- MEDLINE
DCOM- 20111031
LR  - 20220310
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 68
IP  - 3
DP  - 2011 Sep
TI  - Sunitinib in combination with paclitaxel plus carboplatin in patients with 
      advanced solid tumors: phase I study results.
PG  - 703-12
LID - 10.1007/s00280-010-1536-1 [doi]
AB  - PURPOSE: To evaluate the maximum tolerated dose (MTD), safety, and antitumor 
      activity of sunitinib combined with paclitaxel and carboplatin. METHODS: 
      Successive cohorts of patients with advanced solid tumors received oral sunitinib 
      (25, 37.5, or 50 mg) for 2 consecutive weeks of a 3-week cycle (Schedule 2/1) or 
      as a continuous daily dose for 3-week cycles (CDD schedule) in combination with 
      paclitaxel (175-200 mg/m(2)) plus carboplatin (AUC 6 mg min/ml) on day one of 
      each of 4 cycles. Dose-limiting toxicities (DLTs) and adverse events (AEs) were 
      evaluated to determine the MTD. Efficacy parameters were analyzed in patients 
      with measurable disease. RESULTS: Forty-three patients were enrolled (n = 25 
      Schedule 2/1; n = 18 CDD schedule). Across all doses, 6 DLTs were observed [grade 
      4 papilledema, grade 5 GI hemorrhage, grade 3 neutropenic infection, and grade 4 
      thrombocytopenia (n = 3)]. The MTD for Schedule 2/1 was sunitinib 25 mg plus 
      paclitaxel 175 mg/m(2) and carboplatin AUC 6 mg min/ml. The MTD was not 
      determined for the CDD schedule. Treatment-related AEs included neutropenia 
      (77%), thrombocytopenia (56%), and fatigue (47%). Of 38 evaluable patients, 4 
      (11%) had partial responses and 12 (32%) had stable disease. PK data indicated an 
      increase in maximum and total plasma exposures to sunitinib and its active 
      metabolite when given with paclitaxel and carboplatin compared with sunitinib 
      monotherapy. CONCLUSIONS: Myelosuppression resulting in prolonged dose delays and 
      frequent interruptions was observed, suggesting that this treatment combination 
      is not feasible in the general cancer population.
FAU - Heath, Elisabeth I
AU  - Heath EI
AD  - Karmanos Cancer Institute, Detroit, MI 48201, USA. heathe@karmanos.org
FAU - Blumenschein, George R Jr
AU  - Blumenschein GR Jr
FAU - Cohen, Roger B
AU  - Cohen RB
FAU - Lorusso, Patricia M
AU  - Lorusso PM
FAU - Loconte, Noelle K
AU  - Loconte NK
FAU - Kim, Sindy T
AU  - Kim ST
FAU - Ruiz-Garcia, Ana
AU  - Ruiz-Garcia A
FAU - Chao, Richard C
AU  - Chao RC
FAU - Wilding, George
AU  - Wilding G
LA  - eng
GR  - P30 CA014520/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 - 20101208
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage
MH  - Antineoplastic Agents, Phytogenic/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Area Under Curve
MH  - Carboplatin/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Endpoint Determination
MH  - Female
MH  - Half-Life
MH  - Hematologic Diseases/chemically induced/epidemiology
MH  - Humans
MH  - Indoles/administration & dosage
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/pathology
MH  - Paclitaxel/administration & dosage
MH  - Pyrroles/administration & dosage
MH  - Sunitinib
MH  - Treatment Outcome
PMC - PMC3400085
MID - NIHMS376064
EDAT- 2010/12/09 06:00
MHDA- 2011/11/01 06:00
PMCR- 2012/07/19
CRDT- 2010/12/09 06:00
PHST- 2010/09/01 00:00 [received]
PHST- 2010/11/15 00:00 [accepted]
PHST- 2010/12/09 06:00 [entrez]
PHST- 2010/12/09 06:00 [pubmed]
PHST- 2011/11/01 06:00 [medline]
PHST- 2012/07/19 00:00 [pmc-release]
AID - 10.1007/s00280-010-1536-1 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2011 Sep;68(3):703-12. doi: 
      10.1007/s00280-010-1536-1. Epub 2010 Dec 8.