A phase II trial of three sequential doublets for the treatment of advanced müllerian malignancies.
OBJECTIVE
In an effort to improve the results of primary chemotherapy for müllerian malignancies a novel chemotherapy program was piloted that delivered three sequential chemotherapy doublets. The primary endpoints were surgically defined response rates and evaluation of toxicity.


METHODS
After primary cytoreductive surgery patients were treated with three sequential doublets including three initial cycles of carboplatin and paclitaxel (doublet 1) and then two cycles of cisplatin (day 1) and gemcitabine (days 1 and 8; doublet 2), and finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet 3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5 mcg/kg/day. After therapy, all women were clinically staged and evaluated by second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for residual disease.


RESULTS
A total of 49 eligible patients were enrolled with a median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2 with papillary serous carcinoma of the uterus. Eighty-four percent of patients had stage IIIc/IV tumors, with 29% having >1 cm residual disease after primary cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A total of 283 cycles of chemotherapy were delivered with acceptable toxicities. There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol hypersensitivity, 1 for gemcitabine pulmonary hypersensitivity, and 1 for serious line infection). Neutropenia, typically without fever, was relatively frequent in the first doublet. Nausea and thrombocytopenia were the predominant toxicities in doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women had restaging results consistent with a clinical complete response (CR) and underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%.


CONCLUSIONS
Treatment with this sequential doublet regimen is feasible with a 38% pathologic CR rate.
Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
U
U
Matulonis
S
S
Campos
L
L
Duska
A
A
Fuller
R
R
Berkowitz
S
S
Gore
M
M
Roche
T
T
Colella
H
H
Lee
M V
MV
Seiden
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; D019772:Topotecan; D004317:Doxorubicin; D016190:Carboplatin; D000093542:Gemcitabine