Paclitaxel progressive disease

Pegylated liposomal doxorubicin is an emerging option for patients with recurrent ovarian cancer. In an early phase II study, 35 patients with progressive disease after at least one platinum and paclitaxel-based regimen received pegylated liposomal doxorubicin 50 mg/m every 3 weeks (with a dose reduction to 40 mg/m in the event of grade 3 or 4 toxicities or a lengthening of the interval to... 

The Eastern Cooperative Oncology Group has studied the combination of high-dose paclitaxel and cisplatin with G-CSF support in comparison to low-dose paclitaxel and cisplatin in a recent phase III trial (77). Patients with locally advanced, recurrent, or metastatic disease were randomly placed on arm A of paclitaxel (200 mg/m2 over a 24-h infusion), cisplatin (75 mg/m2), and G-CSF (starting d 3 until the ANC was >10,000/pL) or armB ofpaclitaxel (135 mg/m2 over a 24-h infusion) and cisplatin (75 mg/m2). The tre atment was repeated every 21 d until progression of disease or a total of 12 cycles. 

Marked increments in response were observed with the incorporation of cisplatin into combination regimens response rates greater that 50% were reported in Phase-Ill studies of cisplatin/ifosfamide, cisplatin/ifosfamide/ bleomycin, and cisplatin/5-FU [188-190]. Randomized trials of these combinations administered prior to radiotherapy in locally advanced disease have not shown a survival advantage however, a recent GOG trial of concurrent cisplatin or cisplatin/5-FU/hydroxyurea and radiation was associated with significantly improved progression-free survival versus concurrent hydroxyurea and radiation in patients with Stage IIB-IVA cervical cancers [191]. Combined cisplatin and paclitaxel produced responses in 9 of 11 patients in a recent GOG study [192] and will be the focus of larger trials in the future. 

Many clinicians now prefer to use docetaxel (licensed to be used in combination with trastuzumab for metastatic breast cancer) instead of paclitaxel as it is more convenient to administer (1 hour infusion for docetaxel instead of 3 hours for paclitaxel) and clinicians generally have more experience of using this agent in breast cancer therapy. The pivotal trial of this combination shows superiority of docetaxel and trastuzumab over docetaxel alone in terms of overall survival, response rate and time to disease progression with little additional toxicity (Marty etal., 2005). 

Doxil (doxorubicin) an anticancer drug for the treatment of metastatic ovarian cancer in patients with disease that is refractory to both paclitaxel-and platinum-based chemotherapy regimens and for the treatment of AIDS-related Kaposi s sarcoma with disease that has progressed. 

The NCCN guidelines recommend three to six cycles of treatment for lower stage tumors and at least six cycles of treatment for patients with stage III or IV disease. However, results of a recent randomized study showed that 12 months of maintenance pachtaxel significantly prolongs the duration of progression-free survival in patients with advanced ovarian cancer who attain a complete response to initial platinum and paclitaxel-based chemotherapy. ... 

A phase III trial examined a total of 462 eligible patients with small (<1 cm in maximal diameter), residual, advanced ovarian cancer who were randomized to receive two comses of either carboplatin (AUC = 9) followed by IV pachtaxel 135 mg/m over 24 honrs and IP cisplatin 100 mg/m every 21 days for six cycles, or IV paclitaxel 135 mg/m over 24 hours and IV cisplatin 75 mg/m every 21 days for six cycles. Progression-free survival was superior in the IP arm versus the IV arm (median 27.9 months vs. 22.2 months, respectively). Overall survival was 63.2 months in the IP arm versus 52.2 months in the IV arm. Although a significant improvement in progression-free survival was observed, toxicity was much greater in the experimental arm. Results from this study provide future direction for clinical studies in patients with smaU-volume disease. ... 

A total of 469 patients were enrolled into a randomized, multicenter, phase III trial of chemotherapy with or without Herceptin [52]. All patients had previously untreated, IHC 2+/3+ MBC. Patients who had previously received anthracyclines in the adjuvant setting were randomized to receive paclitaxel (175 mg m 3-weekly) alone (n=96) or with Herceptin (n=92). All other patients were randomized to receive anthracycline (doxorubicin 60 mg m or epirubicin 75 mg m ) plus cyclophosphamide (600 mg m ) alone (n=138) or with Herceptin (n=143) (Fig. 5.7). The primary endpoint was TTP. Secondary endpoints were ORR, DR, TTF, OS and 1-year survival. An independent RFC determined disease progression and response. 

---