Fallopian Tube Cancer Treatment Protocols

Fallopian tube carcinomas were once believed to be rare. However, investigators have demonstrated precursor cancerous lesions in the fallopian tube (tubal in-situ carcinoma [TIC]) and have provided evolutionary evidence that many advanced serous ovarian cancers originate in the fallopian tubes. ^{[1, 2]} Currently, both early-stage and advanced-stage fallopian tube cancers are treated in much the same way as ovarian cancers—that is, with surgery followed by chemotherapy. ^[3]

Surgery is the initial therapy for stage I-IV fallopian tube cancers. Only a small percentage of women with epithelial fallopian tube cancers are treated with surgery alone. In fact, most patients with stage I disease are treated with adjuvant chemotherapy because of the luminal structure of the organ and the risk of shedding cells out of the tubes and into the abdominal cavity.

The goals of surgical intervention include both staging and tumor debulking. Staging fallopian tube cancer involves the removal of both fallopian tubes and of the ovaries, uterus, cervix, infracolic omentum, and retroperitoneal lymph nodes, in addition to peritoneal washings and peritoneal biopsies.

The data regarding the treatment of fallopian tube cancers are limited and extrapolated from the ovarian cancer literature; no randomized trials have specifically addressed fallopian tube cancers. Accordingly, the chemotherapy used to treat primary fallopian tube cancers is based on the standard management of ovarian cancers.

Consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) suggest administering three to six cycles of chemotherapy for stage IA-IC disease and six to eight cycles for stage II-IV disease. ^[4] Many physicians feel that administering six cycles of treatment is more appropriate in this disease. As in ovarian cancer, the use of intraperitoneal (IP) chemotherapy must be considered the current standard treatment option in patients with stage II-IV disease.

In the treatment recommendations below, note that carboplatin is dosed to achieve a targeted area under the curve (AUC), which is defined as the area under the concentration-versus-time curve and expressed in mg/mL/min. The calculation is based on the Calvert formula ^[5] (see the Carboplatin AUC Dose Calculation (Calvert formula) calculator). The maximum dose is based on the maximum estimated glomerular filtration rate (GFR).

Treatment recommendations for stage I disease

Treatment recommendations for stage I fallopian tube cancer include the following:

• 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 ^[6]  or

• Docetaxel 60-75 mg/m² IV infused over 1h plus  carboplatin AUC 5-6 IV infused over 1 h every 21 d for three to six cycles ^{[6, 7]}

Treatment recommendations for stage II-III disease

Patients who have undergone optimal tumor debulking should be offered IP chemotherapy. The following dosing regimen is recommended:

• Paclitaxel 135 mg/m² IV infused over 24 h on day 1 (may be given over 3 h if tolerated) plus cisplatin 100 mg/m² IP on day 2 (may be reduced to 75 mg/m² and given on day 1 or  day 2 to allow an outpatient regimen) plus  paclitaxel 60 mg/m² IP on day 8 every 21 d for six cycles ^{[8, 9, 10]}

Treatment recommendations for stage II-IV disease

If the patient is unable to tolerate IP chemotherapy, debulking has been suboptimal (ie, disease >1 cm), disease has spread to the liver parenchyma, or the patient has malignant plural effusions, one of the following IV regimens should be considered:

• 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 six cycles ^[11]  or

• Dose-dense paclitaxel 80 mg/m² IV Days 1, 8, and 15 followed by  carboplatin AUC 5–6 IV Day 1  every 21 days for six cycles ^{[4, 12, 13]}

• Docetaxel 60-75 mg/m² infused over 1 h plus  carboplatin AUC 5-6 IV infused over 1 h every 21 d for three to six cycles ^[7]

Treatment recommendation for recurrent disease

Platinum-sensitive disease:

A disease-free interval of at least 6 months constitutes platinum-sensitive disease. These patients have been re-treated with platinum-based chemotherapy. Most patients are re-treated with a platinum doublet. Single-agent treatment is the preferred approach for platinum-resistant patients or intermediate platinum-sensitive patients with a short time to recurrence (6-12 months).

• 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 ^{[8, 14]}  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 ^{[7, 14]}  or

• Pegylated liposomal doxorubicin 30 mg/m² IV infused over 30 min plus carboplatin AUC 5 IV every 21 d for six cycles ^{[15, 16]}  or

• Gemcitabine 1000 mg/m² IV on days 1 and 8 plus  carboplatin AUC 4 on day 1 every 21 d for six cycles ^[17] or

• Carboplatin AUC 6 IV push once every 3 weeks with paclitaxel 80 mg/m² IV infused over 3 h every week ^[18]

Consideration may be given to bevacizumab, in combination with carboplatin and paclitaxel ^[19] or with carboplatin and gemcitabine ^[20] , 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 ^[19]   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 ^[20]

Platinum-resistant disease:

For a recurrence that develops less than 6 months after the completion of initial therapy, one of the following single-agent regimens may be considered:

• Pegylated liposomal doxorubicin 50 mg/m ² IV infused over 30 min every 21 d ^[21]   or
• Topotecan 1.25 mg/m ² IV infused over 30 min on days 1-5 every 21 d ^[21]   or
• Gemcitabine 1000 mg/m ² IV infused over 30 min on days 1 and 8 every 21 d ^[22]
• Other agents listed in the NCCN guidelines ^[4]

In November 2014, the US Food and Drug Administration (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. ^[23]  

The bevacizumab regimen consists of 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) ^[23]  or

• Bevacizumab 15 mg/kg IV every 21 d in combination with topotecan (every 21 d) ^[23]

Secondary cytoreductive surgery:

The role of cytoreductive surgery continues to be explored in patients with recurrent disease. If more than 6 months has passed from complete clinical response to therapy, reoperation can be considered. ^[24]

Maintenance therapy

The FDA has approved three poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) enzyme inhibitors for maintenance treatment of recurrent fallopian tube cancer in women who are in complete or partial response to platinum-based chemotherapy, as follows:

• Olaparib (Lynparza) 300 mg PO BID until disease progression or unacceptable toxicity
• Niraparib (Zejula) 600 mg PO BID until disease progression or unacceptable toxicity
• Rucaparib (Rubraca) 300 mg PO daily until disease progression or unacceptable toxicity

Special considerations

See the list below:

• The AUC for treatment of fallopian tube cancers ranges from 5 to 7.5 and may be as low as 4 in patients who have limited functional status or have previously undergone treatment with chemotherapy and radiation. ^[25]
• Antiangiogenic agents (eg, bevacizumab) may be beneficial in front-line therapy, maintenance, or recurrent disease and are being explored in ongoing studies. ^{[26, 20, 27]}
• Neoadjuvant chemotherapy may be appropriate in patients who are unable to tolerate up-front debulking or those with stage IV disease. ^{[28, 29]}