Efficacy and safety of pegylated liposomal doxorubicin in primary cutaneous B‐cell lymphomas and comparison with the commonly used therapies

Abstract

Doxorubicin is frequently used in the treatment of lymphomas; the pegylated liposomal formulation of the drug (Peg-Doxo) has significantly improved its therapeutic index, reducing the toxic adverse effects. Peg-Doxo shows a similar efficacy, being less cardiotoxic, producing less nausea and vomiting and only mild myelosuppression and alopecia (1). The drug, carried in stealth liposomes able to escape the interception by the immune system, shows a prolonged circulation time and a propensity for extravasating through the leaky vessels of the tumour tissues; it results the increased concentration of the drug in target tissues and the decreased toxicity to normal cells (2). Originally approved for the treatment of metastatic breast cancer, in advanced ovarian cancer and in Kaposi's sarcoma, Peg-Doxo has AbstractObjectives: The therapy of advanced, relapsed or refractory primary cutaneous lymphomas is often unsatisfactory. Recent data indicate a favourable pharmacokynetic, pharmacodynamic and toxicity profile of pegylated liposomal doxorubicin (Peg-Doxo) in primary cutaneous T-cell lymphomas, while in primary cutaneous B-cell lymphomas (PCBCLs), the drug efficacy has never been assessed so far. Methods: We performed a prospective phase II pilot clinical trial of Peg-Doxo monotherapy (20 mg ⁄ m 2 ) in PCBCLs. One patient had a marginal zone B-cell lymphoma and four were affected by diffuse large B-cell lymphoma-leg type, all with widespread nodular lesions. Results: All the patients achieved a complete response (CR = 100%) in a short period of time (median 3 months), even when pretreated with radio-chemotherapy. Two experienced a relapse. At follow-up, one patient died for progressive disease; four are in CR after 5, 52, 63 and 69 months. As concerning the toxicity profile, the treatment was well-tolerated, no one decreased or delayed the dose. The haematological toxicity was mild with only one case of grade III neutropenia; a patient showed a grade I neurotoxicity. Dermatological toxicity, in particular the palmarplantar erythrodysesthesia, did not occurred, probably because of both the low dosages of Peg-Doxo monotherapy and the oral prophylaxis with pyridoxine. Conclusions: In spite of the small number of patients, it emerges that monochemotherapy with Peg-Doxo has a significantly high clinical activity and a good safety profile in PCBCLs, even in aggressive forms, compared with other therapeutic regimens, which are completely reviewed. It suggests the need of further investigations in this field.

Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells

“…There is also a substantial amount of literature demonstrating the beneficial properties of liposomal chemotherapeutics in the preclinical settings. For instance, liposomal formulations of anthracycline chemotherapeutics and gemcitabine have led to a marked improvement in tumoricidal activity (Cosco et al, 2009a, Paolino et al, 2010, Pulini et al, 2009). …”

Menopause doch kein KHK-Risikofaktor

“…Die Dosis war mit 20 mg/m 2 niedrig gewählt. In Folgestudien soll dieses nebenwirkungsarme und einfach zu applizierende Medikament an einer hö-heren Fallzahl weiter untersucht werden [37]. …”

Pegylated liposomal-encapsulated doxorubicin in cutaneous composite lymphoma

“…Reported overall response rates, that is, complete response (CR) plus partial response (PR), range from 20 % to 44 % in CTCL of MF or Sezary type. [ 5–9 ] Interestingly, PLE-DOXO has shown activity in a phase II trial for primary cutaneous B cell lymphoma as well [10] …”