Clinical efficacy and prospects for use of pegylated liposomal doxorubicin in the treatment of ovarian and breast cancers

There is an urgent need for more active and better tolerated chemotherapy regimens for the treatment of advanced breast and ovarian cancers. Current therapeutic strategies in these malignancies include the use of moderately effective initial regimens that are usually accepted by patients. Tolerabili...

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Bibliographic Details
Published in:Drugs (New York, N.Y.) N.Y.), 1997, Vol.54 Suppl 4, p.22
Main Author: Muggia, F M
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - administration & dosage
Breast Neoplasms - drug therapy
Breast Neoplasms - economics
Breast Neoplasms - psychology
Clinical Trials as Topic
Doxorubicin - administration & dosage
Drug Carriers
Drug Delivery Systems
Female
Humans
Liposomes - chemistry
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - economics
Ovarian Neoplasms - psychology
Polyethylene Glycols
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Summary:There is an urgent need for more active and better tolerated chemotherapy regimens for the treatment of advanced breast and ovarian cancers. Current therapeutic strategies in these malignancies include the use of moderately effective initial regimens that are usually accepted by patients. Tolerability considerations are especially important in the development of palliative regimens: retreatment for persistent or hormone-resistant disease must include quality-of-life analyses. Pegylated liposomal doxorubicin (PLD) has demonstrated a better therapeutic index than free doxorubicin in murine solid tumours and human tumour xenografts in nude mice. In early clinical studies in patients with refractory ovarian cancer, PLD has produced high response rates (26%) and gratifyingly long response durations (8 to 21 + months after onset of therapy). Less mature data also suggest that PLD is active against breast cancer. Information from these same clinical studies confirms the marked reduction in several toxicities associated with free doxorubicin, including nausea and vomiting, myelosuppression and cardiotoxicity. Alopecia is also markedly diminished. On the other hand, mucosal and skin toxicities appear to be more common with PLD. PLD therefore offers the prospect of retaining activity, together with attenuated acute toxicity. In addition to facilitating the development of palliative regimens with better tolerability, the drug may lend itself to effective integration of chemotherapy with loco-regional therapies; utilisation in 'maintenance' regimens that are associated with an acceptable quality of life for the patient, and the avoidance of long term toxicities associated with treatment. Moreover, additional study of PLD in combination with other drugs and modalities may extend the use of the drug beyond palliation to the development of combination regimens with other drugs at conventional doses, and high doses with G-CSF support.
ISSN:0012-6667
1179-1950
DOI:10.2165/00003495-199700544-00006