Primary Peritoneal Cancer Treatment Protocols

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 ^{[1, 2, 3]} :

• 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

Intravenous 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, ^[4] [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 ^{[3, 5]} or

• 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 ^[6]

Treatment of recurrent disease

Platinum-sensitive 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 ^[5] or

• 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 ^[6] or

• Pegylated liposomal doxorubicin 30 mg/m² IV infused over 30 min plus  carboplatin AUC 5 IV every 21 d for six cycles ^[7] or

• Gemcitabine 1000 mg/m² IV on days 1 and 8 plus  carboplatin AUC 4 on day 1 every 21 d for six cycles ^[8] or

• Carboplatin AUC 2 IV push with paclitaxel 80 mg/m² IV infused over 3 h on days 1, 8, and 15 ^[9]

Consideration may be given to bevacizumab, in combination with carboplatin and paclitaxel ^[10] or with carboplatin and gemcitabine ^[11] , 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 six cycles and up to eight cycles, followed by continued use of bevacizumab 15 mg/kg every 21 days as a single agent ^[10] or
• 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 six 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 ^[11]

Poly adenosine diphosphate-ribose polymerase (PARP) inhibitors are approved as maintenance treatment for recurrent primary peritoneal cancer in adult patients with a complete or partial response to platinum-based chemotherapy:

• Olaparib 300 mg PO BID continued until disease progression or unacceptable toxicity ^[12]
• Niraparib 300 mg PO BID continued until disease progression or unacceptable toxicity ^[13]
• Rucaparib 600 mg PO BID continued until disease progression or unacceptable toxicity ^[14]

Platinum-resistant disease

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 ^{[15, 16]} or

• Topotecan 1.25 mg/m² IV infused over 30 min on days 1-5 every 21 d ^[15] or

• Gemcitabine 1000 mg/m² IV infused over 30 min on days 1 and 8 every 21 d ^[17] or

• Rucaparib 600 mg PO BID continued until disease progression or unacceptable toxicity; indicated for treatment of adult patients with cancer associated with a deleterious BRCA mutation (germline and/or somatic) who have been treated with 2 or more chemotherapies ^[18]
• Niraparib 300 mg PO BID continued until disease progression or unacceptable toxicity; inidcated for patients who have been treated with ≥3 prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)–positive status, defined by either a suspected or deleterious BRCA mutation or genomic instability, and whose disease have progressed > 6 months after response to the last platinum-based chemotherapy ^[18]

Bevacizumab (Avastin) is indicated for platinum-resistant, recurrent peritoneal cancers in patients who received no more than two prior chemotherapy regimens. It is used in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan.

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) ^[19] or

• Bevacizumab 15 mg/kg IV every 21 d in combination with topotecan (every 21 d) ^[19]

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. ^[20]

Special considerations

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. ^[21]

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. ^{[22, 11]}

Neoadjuvant chemotherapy may be appropriate in patients who are unable to tolerate up-front debulking. ^[23]

The use of weekly paclitaxel is being studied in regimens such as the following: ^[24]

• Weekly carboplatin AUC 6 IV push once every 3 wk plus  paclitaxel 80 mg/m² IV infused over 3 h every week