A phase 2 trial of flavopiridol (Alvocidib) and cisplatin in platin-resistant ovarian and primary peritoneal carcinoma: MC0261.
OBJECTIVE
Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers.


METHODS
A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression>vs. ≤6 months following prior platin-based therapy). Measurable disease (RECIST)--or evaluable disease plus CA125>2X post-treatment nadir--and ECOG performance≤2 were required.


RESULTS
Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual.


CONCLUSIONS
The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study.
Division of Medical Oncology, Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA. bible.keith@mayo.edu
Keith C
KC
Bible
Prema P
PP
Peethambaram
Ann L
AL
Oberg
William
W
Maples
David L
DL
Groteluschen
Matthew
M
Boente
Jill K
JK
Burton
Leigh C
LC
Gomez Dahl
Jennifer D
JD
Tibodeau
Crescent R
CR
Isham
Jacie L
JL
Maguire
Viji
V
Shridhar
Andrea K
AK
Kukla
Kalli J
KJ
Voll
Mathew J
MJ
Mauer
Alexander D
AD
Colevas
John
J
Wright
L Austin
LA
Doyle
Charles
C
Erlichman
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D002945:Cisplatin