pirarubicin and Endometrial-Neoplasms

The circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, tumor control, and host survival. Optimally timed cancer chemotherapy with doxorubicin or pirarubicin (06:00h) and cisplatin (18:00h) enhanced the control of advanced ovarian cancer while minimizing side effects, and increased the response rate in metastatic endometrial cancer. Therapy of metastatic bladder cancer with doxorubicin-cisplatin was made more tolerable by this same circadian approach resulting in a 57% objective response rate. This optimally timed therapy is also effective in the adjuvant setting, decreasing the expected frequency of metastasis from locally advanced bladder cancer. Circadian fluorodeoxyuridine (FUDR) continuous infusion (70% of the daily dose given between 15:00h and 21:00h) has been shown effective for metastatic renal cell carcinoma resulting in 29% objective response and stable disease of more than 1 yr duration in the majority of patients. Toxicity is reduced markedly when FUDR infusion is modulated to circadian rhythms. In a multicenter trial in patients with metastatic renal cell cancer, patients were randomized to a flat or a circadian-modified FUDR infusion. This study confirmed a significant difference in toxicity and dose intensity, favoring the circadian-modified group. Hormone refractory metastatic prostate cancer has been treated with circadian-timed FUDR chemotherapy; however, without objective response. Biological agents such as interferon-alpha and IL-2 have shown low but effective disease control in metastatic renal cell cancer, however, with much toxicity. Each of these cytokines shows circadian stage dependent toxicity and efficacy in model systems. In summary, the timing of anthracycline, platinum, and fluoropyrimidine-based drug therapies during the 24h is relevant to the toxic therapeutic ratio of these agents in the treatment of gynecologic and genitourinary cancers.

Topics: Animals; Antineoplastic Agents; Carcinoma, Renal Cell; Cell Cycle; Chronotherapy; Circadian Rhythm; Cisplatin; Doxorubicin; Endometrial Neoplasms; Female; Floxuridine; Genital Neoplasms, Female; Humans; Kidney Neoplasms; Male; Ovarian Neoplasms; Prostatic Neoplasms; Rats; Urinary Bladder Neoplasms; Urogenital Neoplasms

From 1986 to 1990, a multicentric phase II study was conducted with pirarubicin, a new semi-synthetic anthracyclin[4'-O-tetrahydropyranyl-adriamycin (THP)]. 87 patients with advanced gynaecological cancers were treated: epidermoid cervical carcinoma (n = 31), adenocarcinoma of the endometrium (n = 28) and ovarian adenocarcinoma (n = 28). THP was administered by short intravenous infusion, for 3 consecutive days, every 3 weeks. The initial dose of THP was 25 mg/m2 day (25% of patients) which was then reduced to 20 mg/m2 day. The average number of courses was 3.7 (range 1-10). The cumulative THP dose was 180 mg/m2 (range 56-594) in cervix and endometrial tumours and 121 mg/m2 (range 58-425) in ovarian tumours. Myelosuppression was the major observed toxicity with grade 3-4 leukopenia and thrombocytopenia in 62 and 19% of the patients, respectively. Severe general complications occurred in 6% of the patients with three fatalities due to infections. Gastro-intestinal side-effects were frequent and usually mild (7% of grade 3 vomiting). 48% of the patients showed alopecia, which was complete in 9 cases (10%). 3 patients experienced cardiac events. No significant antitumoral activity was observed in patients who had failed to respond to previous chemotherapy. Promising antitumoral activity was noticed in untreated cervico-uterine carcinomas with 19% partial responses and 12% complete responses (CR). THP activity was lower in endometrial carcinomas (9.5% CR). Results were found to be negligible in ovarian cancer patients, most of them being refractory to previous chemotherapy containing an anthracyclin compound. On the basis of these results, the definite role of THP in gynaecological cancers deserves to be studied in more favourable programmes (e.g. in combined protocols as first-line chemotherapy).

Topics: Adenocarcinoma; Adult; Aged; Alopecia; Antineoplastic Agents; Doxorubicin; Endometrial Neoplasms; Female; Humans; Leukopenia; Middle Aged; Ovarian Neoplasms; Thrombocytopenia; Uterine Cervical Neoplasms; Vomiting

Although anthracyclines are considered as being among the most potent chemotherapeutic agents for endometrial carcinoma, the majority of institutions in Japan prefer a combination of paclitaxel and carboplatin (TC) for treating this disease. We retrospectively evaluated the efficacy and feasibility of combined paclitaxel, pirarubicin, and carboplatin (TPC) therapy for endometrial carcinoma.. Thirty-nine patients with high/intermediate postoperative recurrence risks or with advanced disease received combination chemotherapy consisting of paclitaxel (150 mg/m(2)), pirarubicin (35 mg/m(2)), and carboplatin [area under the concentration time curve (AUC = 4)] from 2001 to 2006 at Okayama University Hospital. Treatment cycles were repeated every 3 weeks, and three to nine cycles were administered according to patient risk.. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 94.9% and 84.6%, respectively, and the 3-year OS and PFS rate was 81.3%. Hematologic toxicities >grade 3 were: anemia 30.8%; leukopenia 84.6%; thrombocytopenia 20.5%. Neutropenia was common, and administration of granulocyte colony-stimulating factor (G-CSF) was necessary in 87.9% of treatment courses. Although grade 3 or 4 neutropenia was unavoidable, we could administer TPC therapy safely and without delay with G-CSF support. Gastrointestinal and neurological toxicity were less severe and less frequent compared with TC, and no cardiac toxicity was observed.. The 3-year PFS and OS rates even in high-risk patients were satisfactory, and we confirmed the feasibility of using this regimen for treating endometrial carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemotherapy, Adjuvant; Disease-Free Survival; Doxorubicin; Endometrial Neoplasms; Feasibility Studies; Female; Humans; Hysterectomy; Japan; Kaplan-Meier Estimate; Lymph Node Excision; Middle Aged; Neoplasm Staging; Paclitaxel; Pilot Projects; Retrospective Studies; Time Factors; Treatment Outcome

To evaluate the validity of administration of paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients with gynecologic cancer, we explored the efficacy and safety of these regimens. From October 1, 1998 to September 30, 2001, we administered paclitaxel and carboplatin with or without THP-ADR pursuant to the chart we prepared originally as first line chemotherapy in patients with gynecologic cancer. Eleven elderly patients (age > 70 years) and 62 younger patients (age < 70 years) were entered into the present study. Paclitaxel was administered as a 3-hour intravenous (i.v.) infusion at dosages of 135 to 180 mg/m2 immediately followed by carboplatin over 60 minutes at dosages of area under the curve (AUC) 3 to 5, administered intravenously or intraperitoneally. We observed grade 3/4 anemia more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin without THP-ADR (9% v.s. 47%, p < 0.0001). Grade 3/4 anemia (10% v.s. 22%, p = 0.02) and grade 3/4 thrombocytopenia (7% v.s. 22%, p = 0.007), febrile neutropenia (14% v.s. 44%, p = 0.02) also occurred more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin with THP-ADR. The overall response rates were equivalent among elderly and younger patients (69% and 78%), respectively. The regimen consisting of paclitaxel and carboplatin without THP-ADR was applied safely to elderly patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Doxorubicin; Drug Administration Schedule; Endometrial Neoplasms; Female; Genital Neoplasms, Female; Humans; Leukopenia; Middle Aged; Neutropenia; Ovarian Neoplasms; Paclitaxel; Retrospective Studies; Taxoids; Thrombocytopenia; Uterine Cervical Neoplasms

Prognosis of patients with stage IVB endometrial adenocarcinoma is quite poor. Combination therapy of radiation with surgery or chemotherapy is a common therapy for advanced endometrial cancers. However, radiation therapy is effective only for localized cancer, and the chemotherapeutic effect on stage IVB endometrial cancers is very low. We present a patient with stage IVB endometrial adenocarcinoma, whose tumor was not resected completely at the first surgery. She showed a remarkable response to a PEP (pirarubicin, etoposide, cisplatin) regimen and has survived without disease over 8 years. This case suggests that reduction surgery following PEP therapy is a new therapeutic modality for stage IVB endometrial carcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Endometrial Neoplasms; Etoposide; Female; Humans; Middle Aged; Neoplasm Staging