Phase II study of i.v. CI-980 in patients with advanced platinum refractory epithelial ovarian carcinoma.
CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine site, inhibiting the polymerization of microtubules and arresting cellular division in metaphase. Myelosuppression and neurotoxicity were dose-limiting in phase I studies. Sixteen patients with stage III and IV platinum-refractory ovarian cancer received 4.5 mg/m2/day of CI-980 as a continuous i.v. infusion for 72 h, repeated every 3 weeks. Eleven patients had progression and four patients had stable disease. One patient (6%; 95% CI 0-25%) achieved a partial response after 9 months of treatment which lasted for 27 months. The overall median survival was 7 months. Grade 4 granulocytopenia occurred in five patients, with two episodes of neutropenic fever. Neurological toxicity was mild with 12 episodes of transient subclinical recent memory loss documented in four patients by specialized neuropsychological evaluations. One patient each had hallucinations and mild truncal ataxia, and four patients had mild, reversible neurosensory toxicity. One episode of severe hypoxemia and dyspnea occurred in a patient with chronic obstructive pulmonary disease. CI-980 has minimal activity and is tolerable in a population of heavily pretreated patients with platinum refractory ovarian cancer.
Kudelka
A P
AP
University of Texas MD Anderson Cancer Center, Houston 77030-4095, USA.
Hasenburg
A
A
Verschraegen
C F
CF
Edwards
C L
CL
Meyers
C A
CA
Varma
D
D
Freedman
R S
RS
Forman
A
A
Conrad
C A
CA
Grove
W
W
Grothey
A
A
Kavanagh
J J
JJ
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced; D007262:Infusions, Intravenous; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010689:Phlebitis / Q000139:chemically induced; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002219:Carbamates; D009944:Organoplatinum Compounds; D011719:Pyrazines; D011725:Pyridines; C072383:canertinib dihydrochloride