A phase Ib and pharmacokinetic trial of patupilone combined with carboplatin in patients with advanced cancer.
OBJECTIVE
Patupilone is a microtubule-targeting chemotherapeutic agent with clinical activity in a broad range of taxane-sensitive/resistant tumor types. The present phase Ib study examined the safety/tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors.


METHODS
Patients with advanced cancer received patupilone via a 5- to 10-min i.v. infusion at doses of 3.6 to 6.0 mg/m(2) q3w, immediately followed by carboplatin area under the curve (AUC) 5 or 6 mg/mL/min.


RESULTS
Of the 37 patients enrolled, the majority previously received taxanes (81%) and/or platinum-containing drugs (97.3%). The maximum tolerated dose (MTD) of patupilone with carboplatin AUC 6 was 4.8 mg/m(2); additional patients were enrolled to consolidate experience at this dose. Of the 22 patients who received the MTD, the most common nonhematologic adverse events were fatigue in six (27.3%) and diarrhea, nausea, vomiting, abdominal pain, and neuropathy in one each (4.5%; all grade 3); hematologic toxicities included two patients (9.1%) with grade 3 neutropenia. The pharmacokinetics of patupilone were similar to those in a previous study of patupilone monotherapy. Of the 26 patients with recurrent platinum-sensitive ovarian cancer, tumor response was assessable by response evaluation criteria in solid tumors in 17; 1 patient (6%) achieved a complete response, and 10 (59%) achieved a partial response.


CONCLUSIONS
The combination of patupilone 4.8 mg/m(2)/carboplatin AUC 6 was well tolerated and showed antitumor activity similar to established regimens in patients with recurrent platinum-sensitive ovarian cancer. The optimal dose for this regimen is currently being further refined in phase II trials.
Forster
Martin
M
Royal Marsden Hospital Gynecology Unit, London, United Kingdom.
Kaye
Stan
S
Oza
Amit
A
Sklenar
Ivo
I
Johri
Anandhi
A
Cheung
Wing
W
Zaknoen
Sara
S
Gore
Martin
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D016190:Carboplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D034261:Epothilones / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000473:pathology
D000970:Antineoplastic Agents; D034261:Epothilones; D016190:Carboplatin; C093788:epothilone B