The recommended doses and schedule for intraperitoneal chemotherapy are paclitaxel 135 mg/m2 intravenous on day 1, followed by cisplatin 75 to 100 mg/m2 intraperitoneal on day 2, followed by paclitaxel 60 mg/m2 intraperitoneal on day 8, every 3 weeks for
Table 37.4 Combination Chemotherapy for Advanced Epithelial Ovarian Cancer: Recommended Regimens
Doxorubicin, liposomal 35–50 IV 3–4
Topotecan 1.0–1.25 IV 1 4.0 IV 3 (daily × 3–5 days)
Etoposide 50 PO 3, days 14–21 ∗Bevacizumab 7.5–15 mg/kg can be added to any of these regimens. aExcept for carboplatin dosing, where AUC—area under the curve—dose calculated by using Calvert formula (Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989;7:1748–1756).bDrugs that can be substituted for paclitaxel if hypersensitivity to that drug occurs; the number of treatments administered as tolerated.
six cycles, as tolerated. (Many centers modified the dose of cisplatin to 75 mg/m2 rather than 100 mg/m2 to reduce toxicity. Others substitute carboplatin (AUC 6) for cisplatin in the regimen.) The impact on outcome of these pragmatic modifications is unknown.
Bevacizumab 7.5–15 mg/kg can be added to any of these intravenous or intraperitoneal chemotherapy regimens.
In patients who cannot tolerate combination chemotherapy, single-agent, intravenously administered carboplatin (AUC 5–6) can be given.
In patients who have a hypersensitivity to paclitaxel or carboplatin, an alternative active drug can be substituted (e.g., docetaxel, nanoparticle paclitaxel, cisplatin). In the case of carboplatin hypersensitivity, desensitization could be attempted.
The treatment of all patients with advanced-stage disease is approached in a similar manner, with modifications based on the overall status and general health of the patient and the extent of residual disease present at the time treatment is initiated.
Maintenance of Complete Clinical Response to First-Line Chemotherapy
Because as many as 80% of women with advanced-stage disease who completely respond to their first-line chemotherapy will ultimately relapse, several trials were conducted that administer a drug to these patients immediately following their primary treatment in an effort to decrease the relapse rate.
Paclitaxel In a study conducted by the GOG and SWOG, 277 women with advanced ovarian cancer who had a complete clinical remission to first-line chemotherapy were randomized to receive 3 or 12 cycles of additional single-agent paclitaxel (175 or 135 mg/m2 every 28 days) (227). Patients were excluded if they developed grade 2 or 3 neurotoxicity during their initial chemotherapy. Because of cumulative toxicity, the mean number of actual cycles of paclitaxel received by the group assigned to receive 12 cycles was 9. The treatment-related grade 2 to 3 neuropathy was more common with longer treatment, 24% versus 14% of patients, respectively.