Brand Name: Doxil
Active Ingredient: doxorubicin HCl liposome injection
Indication: Treatment of metastatic ovarian cancer in patients with the disease that is refractory to both paclitaxel- and platinum-based chemotherapy
Company Name: ALZA Pharmaceuticals
Availability: Not approved for marketing as of Aug 99
Doxil was previously approved for the treatment of AIDS-related Kaposi’s sarcoma in patients with disease that has progressed in spite of prior chemotherapy or in patients who are unable to tolerate therapy. On June 28, 1999, Doxil was granted accelerated approval for a new indication, for treatment of patients with metastatic ovarian cancer who did not respond to paclitaxel- and/or platinum-based chemotherapy. Full approval is expected once the time to progression and survival endpoint data are obtained from an ongoing Phase III, 400-patient trial.
How it Works
Doxorubicin HCl is a cytotoxic anthracycline antibiotic associated with a hydrogen chloride radical. The molecule is encapsulated in STEALTH liposomes, which are formulated with surface-bound methoxypolyethylene glycol (MPEG). The STEALTH liposomes that surround Doxil allow the drug to circulate in the blood for extended periods of time. It is believed that Doxil’s effectiveness is due to its small size, which enables the drug molecules to enter the vasculature of tumors. Once inside the tumor, Doxil binds to DNA and inhibits nucleic acid synthesis.
Doxil: Clinical Study Results
One hundred and forty-six patients were included in three open-label studies. All patients had metastatic ovarian carcinoma that was refractory to paclitaxel- and platinum-based chemotherapy. Patients were classified as having refractory carcinoma if the disease progressed during treatment or within six months of treatment completion. All the participants in the three studies were administered 50mg/m2 infused over one hour every three to four weeks for three to six cycles.
The response rate of the refractory patients was the primary efficacy endpoint. Response was assessed using the Southwest Oncology Group (SWOG) criteria. Each response assessment required confirmation four weeks after the initial observation. Secondary efficacy parameters included time to response, duration of response, and time to progression. The response rates for three studies were 22.2% (95% confidence interval [CI]; 8.6% – 42.3%), 17.1% (95% CI; 9.7% – 26%), 0% (95% CI; 0% – 9.7%). The combined response rate of the three studies was 13.8% (95% CI; 8.1% – 19.3%). Data from the three studies were combined to determine the median time to progression, the median time to response, and the duration of response (15.9 weeks, 17.6 weeks, and 39.4 weeks, respectively).
What the Patient Should Know
The following adverse events were reported during the above clinical studies: hand-foot syndrome, stomatitis, and neutropenia. Nausea, vomiting, tiredness, weakness, rash, and mild hair loss should be reported to the patient’s physician.