What is the role of chemotherapy in the treatment of ovarian cancer?

Updated: Aug 10, 2020
  • Author: Andrew E Green, MD; Chief Editor: Yukio Sonoda, MD  more...
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Answer

Only a small percentage of women with epithelial ovarian cancer can be treated with surgery alone. These include patients with stage IA grade 1 and stage IB grade 1 serous, mucinous, and endometrioid tumors. Clear-cell carcinomas are associated with a significantly worse prognosis in stage I, and patients with this histologic subtype should be considered for chemotherapy at all stages.

Patients not treated with chemotherapy should be monitored closely at regular intervals with clinical examination, serum CA-125 estimation, and ultrasonography if an ovary is still present. Surgery to remove the uterus and residual ovary should be considered when the patient no longer desires to remain fertile.

Higher-risk early-stage disease includes all histologic subtypes with stage IA and stage IB grade 3 or IC any grade These patients are usually treated with front-line chemotherapy with a taxane/platinum combination for a minimum of three courses. They should consider participating in clinical trials. Patients with IA and IB, grade 2 disease may also be candidates for chemotherapy. All patients with stage II cancer and greater should receive front-line chemotherapy or consider participation in clinical trials.

The NCCN recommends three to six cycles of intravenous taxane/carboplatin adjuvant chemotherapy for high-risk stage IA, IB, or IC epithelial ovarian cancer. [45] For stage II-IV disease, the recommended options include intraperitoneal chemotherapy, in patients with < 1 cm optimally debulked stage II and III disease; or intravenous taxane/carboplatin for six cycles. In addition, completion surgery, as indicated by tumor response and potential resectability, may be used in selected patients. [45]

Carboplatin is given at an area under the curve (AUC) of 6-7.5 mg/mL/min, using the Calvert formula for calculating total dose of carboplatin: Total dose (mg) = target AUC x (GFR + 25), where GFR = glomerular filtration rate, taken to be the creatinine clearance in mL/min and AUC in mg/mL/min. In patients who have received extensive prior chemotherapy or radiation, treatment should start at an AUC of less than 5.

Paclitaxel and docetaxel are usually dosed at 175 mg/m2 and 60-75 mg/m2 respectively. Cisplatin at 50-75 mg/m2 can be substituted for carboplatin. Increasing the dose intensity of cisplatin did not improve progression-free survival or overall survival compared with standard chemotherapy. [64] Docetaxel in combination with carboplatin has been shown to provide equivalent survival rates with less neurotoxicity but greater neutropenia.

Either cisplatin or carboplatin may be combined with paclitaxel. Randomized studies have proven that both regimens result in equivalent survival rates. However, because of a more tolerable toxicity profile, the combination of carboplatin and paclitaxel is preferred. If patients are treated with cisplatin, paclitaxel should be administered as a 24-hour infusion to decrease the risk of neurotoxicity. Another alternative is to combine carboplatin with docetaxel.

The combination of paclitaxel and carboplatin is customarily given every 3 weeks (day 1 of a 21-d cycle). Because adding other drugs to this regimen has proved disappointing, investigators have studied the use of a dose-dense regimen, in which paclitaxel is given on days 1, 8, and 15 and carboplatin on day 1. [65, 66] The dose-dense regimen has resulted in longer median progression-free survival and higher overall survival. Early discontinuance may be more common with the dose-dense regimen, and increased toxicity has been reported.

A study by Morgan et al found that first-cycle maximum tolerated dose of intraperitoneal carboplatin combined with intravenous paclitaxel did not predict the tolerability of the regimen over multiple cycles. An intraperitoneal dose of carboplatin, at an AUC of 6, in combination with paclitaxel can be administered with a high rate of completion over multiple cycles. Neutropenia is a frequent dose-limiting toxicity; thus, adding hematopoietic growth factors may permit a high completion rate while maintaining this dose. [67]

In a study by Kurtz et al, patients aged 70 years or older experienced more neuropathy and had a higher incidence in the carboplatin-paclitaxel group. [68] As with all study patients, the therapeutic index was better among elderly women with platinum-sensitive recurrent ovarian cancer who received carboplatin-pegylated liposomal doxorubicin than among those who received carboplatin-paclitaxel.

A meta-analysis suggests that postoperative platinum-based chemotherapy prolongs both progression-free survival and overall survival in the majority of patients with early-stage ovarian cancer. However, these authors also noted strong evidence that optimal surgical staging identifies patients who are at low risk and have little or nothing to gain from adjuvant chemotherapy. [69]

A phase III study by Pignata et al found that, compared with standard therapy using carboplatin plus paclitaxel, treatment with carboplatin plus pegylated liposomal doxorubicin produced a similar response rate but a different pattern of toxicity—less neurotoxicity and alopecia but more hematologic adverse effects. These authors conclude that carboplatin plus pegylated liposomal doxorubicin could be an alternative regimen. [70]


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