Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma.
OBJECTIVE
Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach.


METHODS
This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators.


RESULTS
Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1-3 disease (44.8%) recurred (average follow-up 28.1 months, range 8-60 months).


CONCLUSIONS
This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.
University of Queensland, Brisbane, Australia.
Andreas
A
Obermair
Linda
L
Mileshkin
Katharina
K
Bolz
Srinivas
S
Kondalsamy-Chennakesavan
Robyn
R
Cheuk
Paul
P
Vasey
David
D
Wyld
Jeffrey
J
Goh
James L
JL
Nicklin
Lewis C
LC
Perrin
Peter
P
Sykes
Monika
M
Janda
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011788:Quality of Life; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D016190:Carboplatin; D017239:Paclitaxel