Surgery followed by chemotherapy or radiation therapy

Several randomized trials by the Gynecologic Oncology Group (GOG) have used doxorubicin because of its known antitumor activity.[4]

Several randomized trials by the Gynecologic Oncology Group (GOG) have used doxorubicin because of its known antitumor activity.[4]

Adding cisplatin to doxorubicin increased response rates and progression-free survival (PFS) when compared with doxorubicin alone. However, adding cisplatin did not affect overall survival (OS).

A three-drug regimen of doxorubicin, cisplatin, and paclitaxel with granulocyte-colony stimulating factor (G-CSF) was significantly superior to cisplatin and doxorubicin, as shown by the following results:[5,6][Level of evidence B3] Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [7,8] and phase II studies [9-12] suggest clinical activity with the combination of platinum chemotherapy and paclitaxel in patients with endometrial cancer and measurable disease either after primary surgery or at recurrence.

A three-drug regimen of doxorubicin, cisplatin, and paclitaxel with granulocyte-colony stimulating factor (G-CSF) was significantly superior to cisplatin and doxorubicin, as shown by the following results:[5,6][Level of evidence B3] Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [7,8] and phase II studies [9-12] suggest clinical activity with the combination of platinum chemotherapy and paclitaxel in patients with endometrial cancer and measurable disease either after primary surgery or at recurrence.

Response rate was 57% with the three-drug regimen, compared with 34% with the cisplatin and doxorubicin regimen.

A three-drug regimen of doxorubicin, cisplatin, and paclitaxel with granulocyte-colony stimulating factor (G-CSF) was significantly superior to cisplatin and doxorubicin, as shown by the following results:[5,6][Level of evidence B3] Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [7,8] and phase II studies [9-12] suggest clinical activity with the combination of platinum chemotherapy and paclitaxel in patients with endometrial cancer and measurable disease either after primary surgery or at recurrence.

PFS was 8.3 months with the three-drug regimen, compared with 5.3 months with the cisplatin and doxorubicin regimen.

A three-drug regimen of doxorubicin, cisplatin, and paclitaxel with granulocyte-colony stimulating factor (G-CSF) was significantly superior to cisplatin and doxorubicin, as shown by the following results:[5,6][Level of evidence B3] Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [7,8] and phase II studies [9-12] suggest clinical activity with the combination of platinum chemotherapy and paclitaxel in patients with endometrial cancer and measurable disease either after primary surgery or at recurrence.

OS was 15.3 months with the three-drug regimen, compared with 12.3 months with the cisplatin and doxorubicin regimen.

A three-drug regimen of doxorubicin, cisplatin, and paclitaxel with granulocyte-colony stimulating factor (G-CSF) was significantly superior to cisplatin and doxorubicin, as shown by the following results:[5,6][Level of evidence B3] Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [7,8] and phase II studies [9-12] suggest clinical activity with the combination of platinum chemotherapy and paclitaxel in patients with endometrial cancer and measurable disease either after primary surgery or at recurrence.

The 3-drug regimen was associated with grade 3 peripheral neuropathy in 12% of patients and grade 2 peripheral neuropathy in 27% of patients.

The phase III, randomized, open-label, noninferiority GOG-0209 trial (NCT000063999) compared the combination of paclitaxel, doxorubicin, cisplatin (TAP), and G-CSF with carboplatin and paclitaxel (TC) in 1,381 women.[13]

The phase III, randomized, open-label, noninferiority GOG-0209 trial (NCT000063999) compared the combination of paclitaxel, doxorubicin, cisplatin (TAP), and G-CSF with carboplatin and paclitaxel (TC) in 1,381 women.[13]

The median OS was 37 months for patients in the TC group and 41 months for patients in the TAP group (hazard ratio [HR], 1.002; 90% confidence interval [CI], 0.9–1.12). The median PFS was 13 months for patients in the TC group and 14 months for patients in the TAP group (HR, 1.032; 90% CI, 0.93–1.15).[13]

The phase III, randomized, open-label, noninferiority GOG-0209 trial (NCT000063999) compared the combination of paclitaxel, doxorubicin, cisplatin (TAP), and G-CSF with carboplatin and paclitaxel (TC) in 1,381 women.[13]

These results led to the use of TC as the standard adjuvant treatment for patients with stages III and IV disease.

The use of cisplatin and doxorubicin compared with whole-abdominal radiation therapy was studied in a trial of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement.[14][Level of evidence A1]

The use of cisplatin and doxorubicin compared with whole-abdominal radiation therapy was studied in a trial of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement.[14][Level of evidence A1]

Results suggest that cisplatin and doxorubicin improved OS, compared with whole-abdominal radiation therapy (5-year survival rate, 55% for cisplatin and doxorubicin vs. 42% for whole-abdominal radiation; adjusted HR, 0.68; 95% CI, 0.52–0.89; P = .02).

Several trials support combination chemotherapy for patients with stage III, stage IV, and recurrent carcinosarcoma.

Several trials support combination chemotherapy for patients with stage III, stage IV, and recurrent carcinosarcoma.

The GOG-108 trial of ifosfamide, with or without cisplatin, as first-line therapy in patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer PFS in the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months).[15][Level of evidence A1]

Several trials support combination chemotherapy for patients with stage III, stage IV, and recurrent carcinosarcoma.

The follow-up GOG-0161 study (NCT00003128) used 3-day ifosfamide regimens (instead of the more-toxic 5-day regimen in the preceding study) for the control and ifosfamide combined with paclitaxel (with G-CSF starting on day 4) for the study arm.[16]

Several trials support combination chemotherapy for patients with stage III, stage IV, and recurrent carcinosarcoma. › The follow-up GOG-0161 study (NCT00003128) used 3-day ifosfamide regimens (instead of the more-toxic 5-day regimen in the preceding study) for the control and ifosfamide combined with paclitaxel (with G-CSF starting on day 4) for the study arm.[16]

The combination regimen produced superior response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and OS (13.5 months vs. 8.4 months). The HR for death also favored the combination regimen (HR, 0.69; 95% CI, 0.49–0.97).[16][Level of evidence A1]

Several trials support combination chemotherapy for patients with stage III, stage IV, and recurrent carcinosarcoma. › The follow-up GOG-0161 study (NCT00003128) used 3-day ifosfamide regimens (instead of the more-toxic 5-day regimen in the preceding study) for the control and ifosfamide combined with paclitaxel (with G-CSF starting on day 4) for the study arm.[16]

In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, there were imbalances between the treatment arms with respect to the sites of disease and the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.