Non-pegylated liposomal doxorubicin for patients with recurrent ovarian cancer: A multicentric phase II trial

Abstract

Abstract.Patients with non-platinum-sensitive recurrent ovarian cancer have a poor prognosis. Non-pegylated liposomal doxorubicin (Myocet ® ) is a promising drug that may be able to improve treatment for such patients. In the current study, patients with recurrent ovarian cancer relapsing within 12 months after primary treatment received non-pegylated liposomal doxorubicin at 75 mg/m 2 d1q22 and 60 mg/m 2 d1q22 after study dose modification, respectively. There were 29 patients enrolled in the trial, and 124 cycles of non-pegylated liposomal doxorubicin were administered in total. All 29 patients were evaluable for toxicity. The clinical benefit rate (defined as the proportion of patients with either complete remission or partial remission, or with stable disease for >6 months) was 50%. The predominant non-hematological toxicity was nausea and vomiting (18 patients, grade I/II), whilst no palmar plantar erythrodysesthesia was observed. In 3 patients, a grade III hematological toxicity occurred, and the treatment schedule was consequently modified to 60 mg/m 2 d1q22. The findings suggest that non-pegylated liposomal doxorubicin administered in a schedule of 60 mg/m 2 d1q22 is well-manageable and is associated with tolerable non-hematological toxicities (predominantly nausea). IntroductionEpithelial ovarian cancer (EOC) is the most lethal type of gynecological malignancy (1). Each year, almost 22,000 new diagnoses of EOC are made in the United States, and ~14,000 mortalities occur due to disease progression (1). The majority of patients in the early stages of the disease are free of any symptoms; thus, the disease is often of an advanced stage when diagnosed (2). Despite efforts made towards the improvement of primary treatment, over two thirds of treated patients relapse and require a sufficient second-line treatment strategy, which is typically palliative (3).In cases of platinum-sensitive relapse, the standard treatment approach for tumor recurrence occurring at ≥12 months after the primary platinum-based chemotherapy is a re-challenge of platinum-containing regimens; several large trials have proven superiority of platinum-based chemotherapy as a second line therapy compared to non-platinum base chemotherapy (4-6). By contrast, patients relapsing within the first 6 months after primary treatment are considered to have platinum-resistant disease, and the treatment options, as well as the prognosis of the patients, are limited (7). Patients who experience tumor recurrence between 6 and 12 months after primary treatment are considered to have partially platinum-sensitive disease (8). Thus, the necessity for active and tolerable drugs for patients with recurrent EOC is urgent, particularly for cases of non-platinum-sensitive relapse.In patients with platinum-refractory EOC, a number of cytostatic agents, including paclitaxel, topotecan and gemcitabine, have been trialled and have demonstrated activity (7-9). Furthermore, pegylated liposomal doxorubicin has been reported to be active and well-tolerable as

A Nanomedicine Structure–Activity Framework for Research, Development, and Regulation of Future Cancer Therapies

“…Nanomedical Products Currently in Clinical Use for the Treatment of Cancer 16,18,19,29−31 DOX (Myocet) does not promote this side effect while maintaining a similar efficacy profile. 55,56 Therefore, conventional non-PEGylated liposomes are not obsolete and have seen more approvals by the US Food and Drug Administration (FDA) and EMA.…”

Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use

“…Doxorubicin is given via intravenous injection or infusion and typically displays a triphasic plasma clearance and a terminal half‐life of 24–36 h . Doxorubicin is used in multidrug regimens in the treatment of cancers including but not limited to solid tumours such as breast cancer, ovarian cancer and osteosarcoma as well as haematopoietic malignancies such as lymphomas and leukaemia …”

Dalbergioidin Ameliorates Doxorubicin-Induced Renal Fibrosis by Suppressing the TGF-βSignal Pathway

“…Doxorubicin (DXR) is an anthracycline glycoside antibiotic that has broad-spectrum antitumor activity against a variety of human solid tumors—such as ovarian, breast, and lung cancers—as well as several other cancers and hematologic malignancies [1–3]. However, DXR does not discriminate between cancer and normal cells and eradicates not only fast-growing cancer cells but also other rapidly growing cells in the body; therefore, its use in chemotherapy has been restricted.…”