Feasibility study of concurrent weekly cisplatin and whole abdominopelvic irradiation followed by doxorubicin/cisplatin chemotherapy for advanced stage endometrial carcinoma: a Gynecologic Oncology Group trial.
OBJECTIVE
A prospective Phase I study to determine toxicity of concurrent weekly intravenous cisplatin/whole abdominopelvic radiation therapy followed by four cycles of intravenous doxorubicin/cisplatin chemotherapy.


METHODS
Ten patients with advanced endometrial cancer confined to the abdominal cavity and/or paraaortic lymph nodes with small residual disease were treated postoperatively with 3000 cGy whole abdominopelvic irradiation combined with 1500 cGy boost to the pelvis or pelvic and aortic fields. Cisplatin 15 mg/m(2) was given every week during irradiation. After completing radiotherapy, patients were to receive doxorubicin 50 mg/m(2) and cisplatin 50 mg/m(2) every 3 weeks for four cycles. Graduated dose reduction and acceleration of the doxorubicin dose were specified depending upon hematologic toxicity. Toxicities were monitored with weekly laboratory studies during treatment and frequent examinations.


RESULTS
Five patients with Stage IIIC (paraaortic node involvement) and five with Stage IVB disease were treated on this study. Acute toxicity during chemoirradiation included one patient with grade 4 neutropenia and one patient with persistent grade 1 thrombocytopenia. Seven patients received chemotherapy after completing radiation therapy, two progressed before chemotherapy, and one had thrombocytopenia. Toxicity during chemotherapy included grade 4 neutropenia in all patients with four having five episodes of febrile neutropenia. Despite doxorubicin dose reductions for hematologic toxicity, three patients exhibited grade 4 neutropenia after both the second and third cycles. One patient developed a small bowel obstruction from radiation therapy that required surgery. There were no treatment-related deaths. Overall median survival was 14 months, with only one long-term survivor free of disease at 58 months.


CONCLUSIONS
Without cytokine support, whole abdominopelvic irradiation and concurrent weekly cisplatin followed by doxorubicin/cisplatin chemotherapy without cytokine support has prohibitive hematologic toxicity.
Soper
John T
JT
Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, USA. soper001@mc.duke.edu
Reisinger
Susan A
SA
Ashbury
Robert
R
Jones
Ellen
E
Clarke-Pearson
Daniel L
DL
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D010865:Pilot Projects; D011446:Prospective Studies
D004317:Doxorubicin; D002945:Cisplatin