Treatment protocols for primary peritoneal cancer are provided below. Because of the disseminated nature of the disease, primary peritoneal cancer is treated with surgical debulking and chemotherapy. Women with any stage of primary peritoneal cancer should be considered for a clinical trial.
Intraperitoneal chemotherapy regimen
Patients who have undergone optimal tumor debulking should be offered intraperitoneal (IP) chemotherapy; the following dosing regimen is recommended
Paclitaxel 135 mg/m2 IV infused over 24 h on day 1 (may give over 3 h if tolerated) plus cisplatin 100 mg/m2 IP on day 2 (may reduce cisplatin to 75 mg/m2 and give on day 1 or day 2 to allow for an outpatient regimen) plus paclitaxel 60 mg/m2 IP on day 8
Administer every 21 d for six cycles
IV chemotherapy regimens
One of the IV regimens should be considered under any of the following circumstances:
The patient is unable to tolerate IP chemotherapy
The disease has been suboptimally debulked (ie, disease > 1 cm)
The disease has spread to the liver parenchyma
The patient has malignant pleural effusions
In the treatment recommendations below, note that carboplatin is dosed to achieve a targeted area under the concentration curve (AUC). AUC is the target area under the concentration versus time curve in mg/mL/min. The calculation is based on the Calvert formula,
[see the Carboplatin AUC Dose Calculation (Calvert formula) calculator]; the maximum dose is based on a maximum estimated glomerular filtration rate (GFR).
Recommendations are as follows:
Paclitaxel 135-175 mg/m2 IV infused over 3 h plus carboplatin AUC 5-7.5 IV infused over 30-60 min every 21 d for three to six cycles
Docetaxel 60-75 mg/m2 IV infused over 1 h plus carboplatin AUC 5-6 IV infused over 1 h every 21 d for three to six cycles
Treatment of recurrent disease
A disease-free interval of at least 6 months constitutes platinum-sensitive disease; in such cases, patients have been re-treated with platinum-based chemotherapy; most patients are re-treated with a platinum doublet. Recommendations are as follows:
Paclitaxel 135-175 mg/m2 IV infused over 3 h plus carboplatin AUC 5-6 IV infused over 1 h every 21 d for six cycles
Docetaxel 60-75 mg/m2 IV infused over 1 h plus carboplatin AUC 5 IV infused over 1 h every 21 d for three to six cycles
Pegylated liposomal doxorubicin 30 mg/m2 IV infused over 30 min plus carboplatin AUC 5 IV every 21 d for six cycles
Gemcitabine 1000 mg/m2 IV on days 1 and 8 plus carboplatin AUC 4 on day 1 every 21 d for six cycles
Carboplatin AUC 2 IV push with paclitaxel 80 mg/m2 IV infused over 3 h on days 1, 8, and 15
Consideration may be given to bevacizumab, in combination with carboplatin and paclitaxel
or with carboplatin and gemcitabine
, followed by bevacizumab alone, as follows:
Bevacizumab (15 mg/kg IV on Day 1)
plus carboplatin IV (AUC 5 on Day 1)
plus paclitaxel (175 mg/m
2 IV on Day 1) every 21 days for 6 cycles and up to 8 cycles, followed by continued use of bevacizumab 15 mg/kg every 21 days as a single agent
Bevacizumab (15 mg/kg IV on Day 1)
plus carboplatin IV (AUC 4 on Day 1)
plus gemcitabine (1000 mg/m
2 IV on Days 1 and 8) every 21 days for 6 cycles and up to 10 cycles, followed by continued use of bevacizumab 15 mg/kg every 21 days as a single agent until disease progression
Single-agent treatment is the preferred approach for patients with platinum-resistant disease or for patients with intermediate platinum-sensitive disease with a short time to recurrence of 6-12 months. Recurrence that occurs less than 6 months after completion of initial therapy can be considered for single-agent treatment, such as the following:
Pegylated liposomal doxorubicin 50 mg/m2 IV infused over 30 min every 21 d
Topotecan 1.25 mg/m2 IV infused over 30 min on days 1-5 every 21 d
Gemcitabine 1000 mg/m2 IV infused over 30 min on days 1 and 8 every 21 d
Other agents listed in the National Comprehensive Cancer Network (NCCN) Compendium
In November 2014, the FDA approved bevacizumab (Avastin) for platinum-resistant, recurrent, epithelial ovarian, fallopian tube, or peritoneal cancers in patients who received no more than two prior chemotherapy regimens. It is indicated in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan.
Approval was based on results from the Phase III AURELIA study, which showed that adding bevacizumab to chemotherapy significantly improved progressive-free survival (PFS) and overall response rate (ORR). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. ORR was 11.8% versus 27.3%, respectively (P = 0.001). The addition of bevicizumab showed a slight trend toward improving overall survival (OS) compared with chemotherapy alone, but it was not significant. The OS hazard ratio was 0.85 (95% confidence index [CI], 0.66 to 1.08; P< 0.174; median OS, 16.6 v 13.3 months, respectively).
Combination regimens with bevacizumab include the following:
Bevacizumab 10 mg/kg IV every 14 d in combination with one of the following IV chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or topotecan (topotecan is given weekly)
Bevacizumab 15 mg/kg IV every 21 d in combination with topotecan (every 21 d)
Secondary cytoreductive surgery:
The role of cytoreductive surgery continues to be explored in patients with recurrent disease; if more than 6 months have passed since complete clinical response to therapy, reoperation can be considered.
The AUC for treatment of fallopian tube cancers ranges from 5-7.5; it may be reduced to an AUC of 4 in patients with limited functional status or patients who have had prior treatment with chemotherapy and radiation.
Antiangiogenic agents (eg, bevacizumab) may be beneficial as front-line therapy, as maintenance therapy, or in cases of recurrent disease, and they are being explored in ongoing studies.
Neoadjuvant chemotherapy may be appropriate in patients who are unable to tolerate up-front debulking.
The use of weekly paclitaxel is being studied in regimens such as the following:
Weekly carboplatin AUC 6 IV push once every 3 wk plus paclitaxel 80 mg/m2 IV infused over 3 h every week