FDA Approval for Gemcitabine Hydrochloride
- Approved for ovarian cancer
- Approved for breast cancer
- Approved for non-small cell lung cancer
- Approved for pancreatic cancer
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On July 14, 2006, the Food and Drug Administration (FDA) granted approval to gemcitabine hydrochloride (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 hydrochloride 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 hydrochloride 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 hydrochloride 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.
On May 19, 2004, the FDA approved gemcitabine hydrochloride 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 gemcitabine hydrochloride and paclitaxel with paclitaxel alone. Gemcitabine hydrochloride 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 gemcitabine hydrochloride 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. Gemcitabine hydrochloride 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 gemcitabine hydrochloride 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 gemcitabine hydrochloride plus paclitaxel regimen were hematologic (neutropenia, anemia and thrombocytopenia). Grade 3 and 4 liver enzyme elevation was also more common with gemcitabine hydrochloride plus paclitaxel treatment. Grade 3 and 4 non-laboratory toxicities associated with gemcitabine hydrochloride plus paclitaxel therapy included fatigue, neuropathy and myalgias.
Non-Small Cell Lung Cancer
In 1996, the FDA approved gemcitabine hydrochloride to be used in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.
In 1996, the FDA approved gemcitabine hydrochloride as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas for patients previously treated with fluorouracil (5-FU).
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.