by Dr. C.H. Weaver M.D. update 6/2020
The United States Food and Drug Administration (FDA) granted full approval for the drug Doxil® to be used for patients who have ovarian cancer and have experienced disease progression or stopped responding while on a platinum-based chemotherapy in 2005. Doxil can be used alone or in combination with other drugs. (1,2)
Ovarian cancer is a malignancy that arises from various different cells within the ovaries. Approximately 25,000 individuals with ovarian cancer are diagnosed in the United States each year. Unfortunately, ovarian cancer often goes undetected until the disease has progressed into the abdomen or spread to other organs. Current treatment includes surgery, chemotherapy and precision cancer medicines identified by NGS - biomarker testing.
The approval for Doxil® is based on improvements in overall survival time and overall response rates. Overall response rates are ~ 20% with Doxil® in patients with advanced disease. Doxil is not typically used as a single drug but combined with other medications.
Doxorubicin is a chemotherapy drug that has been used for many years to treat ovarian cancer, as well as many other types of cancers. Doxil® consists of fat bubbles (liposomes) that contain doxorubicin, as well as an additional protective layer of glycol strands that protect the liposomes. When doxorubicin is administered, normal cells as well as cancer cells are affected and then the body quickly excretes it. Doxil® is designed to stay in the blood much longer due to the protective mechanisms of the drug’s design. This extended activity allows for increased exposure of the cancer cells to the chemotherapy. In addition, because Doxil® is slowly released over time, treatments are needed less frequently than with doxorubicin. Doxil® may also have less heart toxicity, which is the major dose-limiting toxicity of doxorubicin.
CA-125 May Not Be Reliable Marker for Response to Doxil® In Ovarian Cancer
According to results presented at an annual meeting on Women’s Cancer™, early CA-125 levels were not consistently reliable as a measure of response to Doxil® in women with recurrent ovarian cancer.CA-125 is a “tumor marker” that can be detected in circulating blood and are often elevated among women with ovarian cancer and among those whose cancer is progressing. Physicians frequently use levels of CA-125 to determine if treatment is working among women with ovarian cancer who are undergoing chemotherapy.
- Among the patients who achieved a complete disappearance of detectable cancer following treatment with Doxil, 50% had an increase in CA-125 level from the beginning of treatment (baseline) to the completion of their first cycle of Doxil. Given these data, the researchers concluded that CA-125 does not appear to be a reliable means of measuring anticancer responses to Doxil or topotecan in recurrent ovarian cancer. The researchers state that further study is necessary to confirm these findings; however, it appears that more accurate ways to measure responses are needed. (7)
Doxil + Gemzar
According to study results published in Gynecologic Oncology, the combination of the chemotherapy agents Gemzar® (gemcitabine) and Doxil® (liposomal doxorubicin) offers promise for the treatment of women with recurrent ovarian cancer.
Researchers in Italy conducted this multi-center phase II study to evaluate the efficacy and safety of the combination of Gemzar and Doxil for the treatment of patients with recurrent ovarian cancer. Participants in the study included women with recurrent ovarian cancer who had previously been treated with a minimum of one platinum regimen (Paraplatin® or Platinol® /paclitaxel (Taxol®).
Each patient in this study was treated with Doxil, followed by Gemzar. Of the 106 patients evaluated, nine (8.5 percent) had a complete response (complete disappearance of detectable cancer), and 27 (25.5 percent) had a partial response (partial shrinking of detectable cancer). Overall survival was longer in platinum-sensitive patients (patients who achieved an anti-cancer response lasting greater than six months to platinum chemotherapy) than in platinum-resistant patients (patients whose cancer either did not respond to platinum-based chemotherapy or whose anti-cancer responses lasted less than 6 months). Median survival was 92 weeks among platinum-sensitive patients and 50 weeks among platinum-resistant patients. In both the platinum-sensitive and the platinum-resistant groups, survival was longer among patients who responded to Gemzar plus Doxil. Twenty patients (18 percent) experienced very low blood cell counts as a result of treatment.
According to another article recently published in Gynecologic Oncology, the chemotherapy combination consisting of Gemzar® and Doxil® is effective for patients with ovarian cancer that has stopped responding to standard therapies.
Researchers from Austria recently conducted a clinical trial to evaluate Gemzar plus Doxil in patients with ovarian cancer that has stopped responding to prior therapy with a standard platinum chemotherapy agent (Platinol or Paraplatin). This study included 31 patients.
- Anticancer responses occurred in 33% of patients.
- Complete disappearances of detectable cancer occurred in 20% of patients.
- Half of the patients were alive with no cancer progression at nearly four months.
- Half of the patients were alive at nearly 16 months.
- Severe side effects included low levels of immune cells, hand-foot syndrome (redness, pain, scaling of the palms of hands or soles of feet), and ulcers of the mouth lining.
With half of patients treated with Doxil/Gemzar alive at 16 months, researchers concluded that this treatment combination provides anticancer responses for ovarian cancer that has stopped responding to platinum therapy
The combination of Gemzar and Doxil is “a valid approach” for patients with recurrent ovarian cancer. Patients with recurrent ovarian cancer may wish to speak with their physician regarding their individual risks and benefits of participation in a clinical trial further evaluating Gemzar/Doxil or other promising therapeutic approaches.
Doxil®/Paraplatin® Effective in Recurrent Ovarian Cancer
According to an article published in the Annals of Oncology, treatment consisting of Doxil® and Paraplatin® (carboplatin) may improve survival in patients with relapsed ovarian cancer.Researchers from France recently conducted a clinical trial to evaluate Doxil plus Paraplatin in the treatment of patients with advanced ovarian cancer that had relapsed following prior platinum and taxane-based regimens. (5)
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- Anticancer responses occurred in 63% of patients.
- Complete disappearances of cancer occurred in 38% of patients.
- Median progression-free survival was 9.4 months.
- Median overall survival was 32 months.
The researchers concluded that the combination of Doxil/Paraplatin appears highly effective for women with ovarian cancer that has relapsed following prior taxane and platinum-based therapies.
Doxil® plus Eloxatin® Highly Active in Recurrent Ovarian Cancer
According to an article published in Gynecologic Oncology, the chemotherapy combination consisting of Doxil® plus Eloxatin® (oxaplatin) provides high anticancer activity in patients with recurrent ovarian cancer. (8)
Researchers from Italy recently conducted a clinical trial to evaluate the effectiveness of Doxil plus Eloxatin in 40 patients with recurrent ovarian cancer.
• Regression of cancer was achieved in 68% of patients.
• Disease stabilization occurred in 30% of patients.
• Median progression-free survival was 9.6 months.
• Median overall survival was 18.3 months.
• The main side effects were low levels of immune cells and changes to the skin on the palms of the hands and soles of the feet.
The researchers concluded that the chemotherapy combination consisting of Doxil and Eloxatin provides significant anticancer activity in patients with recurrent ovarian cancer.
Doxil® Superior to Topotecan in Recurrent Ovarian Cancer
A phase III study indicates that for patients with recurrent epithelial ovarian cancer, treatment with Doxil® significantly prolongs survival when compared to treatment with the drug topotecan. (4)
In this study, 474 patients with epithelial ovarian cancer who had recurrent disease or who had failed treatment with platinum-based chemotherapy were randomized to 50mg/m2 of PLD every 28 days or 1.5mg/m2/day of topotecan for 5 days every 21 days. Nearly all of the patients (70%) had had prior treatment with platinum and taxane-containing chemotherapy regimens.
The average overall survival among the 239 patients treated with PLD was 63 weeks. The average overall survival for the 235 patients that received topotecan was 60 weeks. These results were consistent among patients who did not have an anti-cancer response to initial treatment with platinum-based drugs, as well as among the patients who had responded to prior platinum chemotherapy. However, further analysis revealed that patients who had responded to previous platinum-based chemotherapy and were subsequently treated with PLD had a 30% reduction in risk of death. For the subgroup of patients who had responded to previous platinum-based therapy, the average survival for the PLD group was 108 weeks compared to 70 weeks for the patients treated with topotecan.
Researchers concluded that PLD is the only non-platinum-based chemotherapy that has produced a distinct survival advantage and should be the first choice for patients who have failed platinum chemotherapy or who have recurrent disease after receiving platinum-based chemotherapy. Patients are encouraged to speak to their physician regarding treatment options.
- Doxil® prescribing information. Available at: doxil.com/common/prescribing_information/DOXIL/PDF/DOXIL_PI_Booklet.pdf. Accessed February 200.
- Food and Drug Administration. Available here. Accessed February 2005.
- Ferrandina G, Paris I, Ludovisi M et al. Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecologic Oncology. 2005;98:267-273.
- Gordon A, et al. Long-Term Survival Advantage for Recurrent Ovarian Cancer Patients Receiving Pegylated Liposomal Doxorubicin (PLD): Results of a Phase 3 Randomized Study. Proceedings from the Chemotherapy Foundations Symposium XXII: Innovative Cancer Therapy for Tomorrow. Presented November 11, 2004. Phoenix, AZ. Abstract #32.
- Ferrero J-M, Weber B, Geay J-F, et al. Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO Phase II trial. Annals of Oncology. 2007; 18: 263-268.
- Petru E, Angleitner-Boubenizeka L, Reinthaller A, et al. Combined PEG Liposomal Doxorubicin and Gemcitabine are Active and Have Acceptable Toxicity in Patients with Platinum-Refractory and -Resistant Ovarian Cancer After Previous Platinum-Taxane Therapy: A Phase II Austrian AGO Study. Gynecologic Oncology. 2006; 102:226-229.
- Coleman R, Herzog T, Barter J, et al. Early increases in CA-125 after treatment with DOXIL or topotecan are not always reflective of response in patients with recurrent ovarian cancer. Proceedings from the 2006 annual Meeting on Women’s Cancer™. March 2006. Abstract 71.
- Recchia F, Saggio G, Amiconi G, et al. A multicenter Phase II study of pegylated liposomal doxorubicin and oxaliplatin in recurrent ovarian cancer. Gynecologic Oncology. 2007; 106:164-169.