Cancer Medications : Gemzar, Hycamtin

by National Cancer Institute

(Page 9 of 18)

Gemzar for Breast Cancer

On May 19, 2004, the FDA approved gemcitabine HCl for injection (Gemzar®, made by Eli Lilly and Company) in combination with paclitaxel for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

Safety and efficacy were demonstrated in one multicenter, multinational, randomized trial in 529 patients comparing the combination of Gemzar and paclitaxel with paclitaxel alone. Gemzar 1250 mg/m2 (intravenous infusion over 30 minutes) was administered on Days 1 and 8 of a 21-day cycle with paclitaxel 175 mg/m2 (intravenous infusion over 3 hours) administered prior to Gemzar on Day 1 of each cycle. Single-agent paclitaxel 175 mg/m2 (intravenous infusion over 3 hours) was administered on Day 1 of each 21day cycle as the control arm.

The primary endpoint of the study was overall survival. Time to documented progressive disease was a co-primary endpoint. Gemzar in combination with paclitaxel resulted in statistically significant improvement in time to documented disease progression (median TtDPD 5.2 months versus 2.9 months, p<0.0001), and overall response rate (RR 40.6 percent versus 22.1 percent, p<0.0001) compared to monotherapy with paclitaxel. The combination of Gemzar plus paclitaxel also showed a strong trend toward improved survival in an interim survival analysis.

The principal Grade 3 and 4 adverse effects of the Gemzar plus paclitaxel regimen were hematologic (neutropenia, anemia and thrombocytopenia). Grade 3 and 4 liver enzyme elevation was also more common with Gemzar plus paclitaxel treatment. Grade 3 and 4 non-laboratory toxicities associated with Gemzar plus paclitaxel therapy included fatigue, neuropathy and myalgias.

Gemzar for Ovarian Cancer

On July 14, 2006, the FDA granted approval to gemcitabine (Gemzar®, made by Eli Lilly and Company) in combination with carboplatin for the treatment of patients with advanced ovarian cancer that has relapsed at least six months after completion of platinum-based therapy.

The approval was based on a single multicenter, international, open-label, randomized trial enrolling 356 ovarian cancer patients whose disease had relapsed at least six months after first-line platinum-based therapy. Patients were randomized to receive either gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle plus carboplatin (AUC 4) administered on day 1 of each cycle (GC) or to receive carboplatin (AUC 5) administered on day 1 of each 21-day cycle (C).

One hundred seventy-eight patients received GC and 178 patients received C. Patients were comparable for age, baseline ECOG performance status, platinum-free interval, and first-line therapy regimen.

GC treatment resulted in a significant improvement in progression-free survival (PFS). Median PFS was 8.6 months for GC-treated patients and 5.8 months for C-treated patients [log rank p=0.0038; hazard ratio 0.72 (95 percent, C.I. 0.57, 0.90)]. A significant improvement in the investigator-assessed overall response rate was demonstrated for the addition of gemcitabine to carboplatin (47 percent versus 31 percent, p=0.0016), but not in the independently reviewed response rate that excluded sonography or physical exam findings (46 percent versus 36 percent, p=0.11).

Approximately 75 percent of patients in each arm received post-study chemotherapy, including 13 of 120 patients on the C treatment arm for whom post-progression chemotherapy drugs were known and who received gemcitabine after progression. No significant difference in overall survival was observed. The median survival was 18.0 months for GC-treated patients compared to 17.3 months for those receiving single-agent carboplatin [p=0.8977, hazard ratio 0.98 (95 percent C.I. 0.78, 1.24)].

Hematologic toxicity was the most frequent adverse event. Grade 4 (CTC) neutropenia, anemia and thrombocytopenia occurred in 29 percent, 6 percent and 5 percent, respectively, of patients receiving GC compared to 1 percent, 2 percent, and 1 percent of those receiving single-agent carboplatin. Red blood cell and platelet transfusions were more common in GC-treated patients. Grade 3 neurosensory toxicity was observed in 1 percent receiving GC and 2 percent of C-treated patients.

Hycamtin

On June 14, 2006, the FDA approved topotecan hydrochloride (Hycamtin®, made by GlaxoSmithKline) in combination with cisplatin for the treatment of stage IVB recurrent or persistent carcinoma of the cervix (cervical cancer) that is not amenable to curative treatment with surgery and/or radiation therapy.

Topotecan was evaluated in women with stage IVB recurrent or persistent cervical cancer in one open-label, multicenter, cooperative group trial. Two hundred ninety-three patients were randomized to six cycles of topotecan 0.75 mg/m2 IV over 30 minutes for three consecutive days (Days 1-3) plus cisplatin 50 mg/m2 IV over one hour on Day 1 every 21 days or to cisplatin alone at the same dose and schedule.

The primary endpoint was overall survival. The median survival was 9.4 months in the topotecan plus cisplatin group and 6.5 months in the cisplatin group (log-rank p = 0.033). The unadjusted hazard ratio was 0.76 (95 percent CI: 0.59, 0.98).

The most common toxicity on the combination arm was myelosuppression. Grade 3-4 hematologic (of the blood or bone marrow) adverse events occurring more commonly in the combination arm included neutropenia (74 percent vs. 2 percent), anemia (40 percent vs. 22 percent), thrombocytopenia (33 percent vs. 3 percent), and febrile neutropenia (18 percent vs. 8 percent). Grade 3-4 nonhematologic adverse events reported more commonly in the combination treatment arm included pain, nausea and vomiting, metabolic-laboratory, and hepatic.

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