PMID- 17285598
OWN - NLM
STAT- MEDLINE
DCOM- 20070501
LR  - 20151119
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 109
IP  - 5
DP  - 2007 Mar 1
TI  - A phase II study of the safety and efficacy of the multidrug resistance inhibitor 
      VX-710 combined with doxorubicin and vincristine in patients with recurrent small 
      cell lung cancer.
PG  - 924-32
AB  - BACKGROUND: Tumors with multidrug resistance (MDR) frequently up-regulate efflux 
      proteins, including MDR-associated protein (MRP-1) and P-glycoprotein (Pgp). MDR 
      represents an obstacle to successful chemotherapy treatment and is reversible in 
      Pgp- or MRP-1-expressing cells by the inhibitor VX-710. A Phase II study was 
      designed to evaluate VX-710 in combination with doxorubicin and vincristine in 
      patients with sensitive, recurrent small cell lung cancer (SCLC). METHODS: 
      Eligible patients had recurrent SCLC after a response to first-line chemotherapy. 
      Stage 1 safety evaluation was completed with planned expansion if 9 responses 
      were confirmed in the first 35 patients. Patients were treated every 21 days 
      until progression or intolerable adverse events (AEs). RESULTS: Thirty-six 
      patients were enrolled from 1998 to 2000. Neutropenia was the major toxicity, 
      occurring in 26 of 36 patients (72%). Neutropenia was more severe (30% vs 20% 
      grade 4) and developed earlier (58% vs 38% in Cycle 1) among the 15 patients who 
      were enrolled prior to an amendment that required neutropenia prophylaxis. Four 
      patients died on study: 2 from infections likely related to therapy and 2 from 
      cancer progression. Seven of 36 patients (19%) had partial responses; 6 patients 
      sustained responses through 6 cycles of treatment, with 1 response lasting 3 
      years. Three additional patients had unconfirmed responses, and 4 patients had 
      stable disease. The median survival was 6 months. No correlative 
      (99m)Tc-sestamibi uptake in tumor tissue was observed with the addition of VX-710 
      in this study. CONCLUSIONS: The addition of VX-710 to doxorubicin and vincristine 
      therapy did not significantly enhance antitumor activity or survival. Although 
      there were durable responses, criteria were not met to proceed with Stage 2 
      expansion.
FAU - Gandhi, Leena
AU  - Gandhi L
AD  - Massachusetts General Hospital, Boston, Massachusetts, USA.
FAU - Harding, Matthew W
AU  - Harding MW
FAU - Neubauer, Marcus
AU  - Neubauer M
FAU - Langer, Corey J
AU  - Langer CJ
FAU - Moore, Melvin
AU  - Moore M
FAU - Ross, Helen J
AU  - Ross HJ
FAU - Johnson, Bruce E
AU  - Johnson BE
FAU - Lynch, Thomas J
AU  - Lynch TJ
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Piperidines)
RN  - 0 (Pyridines)
RN  - 3KG76X4KJK (biricodar)
RN  - 5J49Q6B70F (Vincristine)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Small Cell/*drug therapy
MH  - Doxorubicin/administration & dosage/adverse effects
MH  - Drug Resistance, Multiple
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Piperidines/administration & dosage/adverse effects
MH  - Pyridines/administration & dosage/adverse effects
MH  - Vincristine/administration & dosage/adverse effects
EDAT- 2007/02/08 09:00
MHDA- 2007/05/02 09:00
CRDT- 2007/02/08 09:00
PHST- 2007/02/08 09:00 [pubmed]
PHST- 2007/05/02 09:00 [medline]
PHST- 2007/02/08 09:00 [entrez]
AID - 10.1002/cncr.22492 [doi]
PST - ppublish
SO  - Cancer. 2007 Mar 1;109(5):924-32. doi: 10.1002/cncr.22492.