A phase I study of ifosfamide, paclitaxel, and carboplatin in advanced and recurrent cervical cancer.
OBJECTIVE
To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer.


METHODS
Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy.


RESULTS
Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2 g/m(2) over 2 h, paclitaxel 175 mg/m(2) over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non-hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath.


CONCLUSIONS
Combination therapy with ifosfamide 2 g/m(2), paclitaxel 175 mg/m(2), carboplatin AUC = 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.
Downs
Levi S
LS
Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. downs008@umn.edu <downs008@umn.edu>
Judson
Patricia L
PL
Argenta
Peter A
PA
Carson
Linda F
LF
Boente
Matthew P
MP
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide