Phase II study of pirarubicin combined with cisplatin in recurrent ovarian cancer

Abstract

Although 50%-80% of patients with advanced ovarian cancer demonstrate an objective response after platinum-based chemotherapy, a majority of these patients will ultimately experience a relapse of their disease. Effective second-line treatment for these patients is of the most importance. We performed a phase II study with cisplatin and pirarubicin (each drug 50 mg/m2 i.v. every 28 days) in 17 patients with relapsed or persistent ovarian carcinoma. All patients had received platinum-containing primary chemotherapy. Overall survival from the time of diagnosis was 38.3 months (45.3 months in relapsed ovarian carcinoma and 28.3 months in ovarian carcinoma persisting after primary chemotherapy). Survival from entrance into the study was 13.0 months (14.2 months in relapsed disease and 11.2 months in refractory disease). Time to progression was 10.3 months. An objective response was observed in 4 patients and another 3 patients had stable disease. Major toxicity consisted of emesis (grade III/IV in 60/64 courses) and myelosuppression WHO grade III/IV in 15 courses. Neurotoxicity occurred in 3 patients and nephrotoxicity in 1 patient. Alopecia occurred in 12 patients. Tachycardia and other low-grade heart toxicities were observed after 5 courses. Dose reduction was necessary because of severe myelosuppression in 4 courses and because of nephrotoxicity in 1 course. Delay of subsequent chemotherapy courses for more than 7 days was necessary after 13 courses and was always due to myelosuppression. The dose-limiting toxicity of combination chemotherapy with cisplatin and pirarubicin is myelosuppression. Response and survival rates are superior in patients with relapsed disease compared to patients with resistant ovarian carcinoma.

Styrene maleic acid copolymer–pirarubicin induces tumor-selective oxidative stress and decreases tumor hypoxia as possible treatment of colorectal cancer liver metastases

“…Doxorubicin is an anthracyline antibiotic that has been used to treat a wide variety of malignancies, including bladder 4 and ovarian cancers, [5][6][7][8] as well as leukemia 9 and lymphoma. 9,10 The use of doxorubicin, however, is limited by acute and chronic cardiotoxicity, 11,12 as well as renal 13,14 and cerebral 15 toxicity.…”

Recent advances in the discovery and development of topoisomerase inhibitors as antitumor agents

“…81 Due to the serious side effects of 74, such as myelosuppression and irreversible cardiotoxicity, pirarubicin [4Ј-O-((R)-tetrahydropyranyl)adriamycin, 120] ( Fig. 23) was developed 82 as a less cardiotoxic analog, and is currently at clinical phase II stage for metastatic breast cancer; [83][84][85] non-Hodgkin's lymphoma; 86 hepatocellular carcinoma; 87 advanced nonsmall cell lung cancer; 88 small cell lung cancer; 89 head and neck carcinoma; 90-92 hormone resistant prostate cancer; 93 cervical, endometrial, and ovarian cancer; 94,95 and advanced pancreatic cancer. 96 Furthermore, many N-salicylidene derivatives 97 and 3Ј-deamino-3Ј-morpholino derivatives 98 of 120 were prepared and biologically evaluated by Ajito et al Most N-salicylidene derivatives were more active than 120 in vitro.…”

Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner

“…THP is primarily used for the treatment of bladder and ureter cancer (1), malignant lymphoma (2), acute leukaemia (3), breast (4) and ovarian cancer (5). The most common side-effect of THP is bone marrow (BM) suppression (as with most anticancer drugs), which primarily manifests as granulocytopaenia (6).…”