pirarubicin and Vomiting

We conducted a randomized controlled study to evaluate the clinical usefulness of (2"R) -4'-O-Tetrahydropyranyladriamycin (THP)-based combination therapy subsequent to induction therapy which was consisted with THP, 5'-DFUR, and CPA in the treatment of advanced or recurrent breast cancer. In maintenance therapy, Arm C received CPA and TAM, and Arm T received these two drugs plus THP. Survival time of 50% for all cases in which maintenance therapy was conducted was 26.9 months in Arm T and 20.9 months in Arm C, showing no significant difference by the log-rank test (p = 0.64). Survival time in all cases in which therapy had been completed was 54.6 months in Arm T and 28.1 months in Arm C, showing a significant difference by the log-rank test (p = 0.03) although the number of cases was few. A few cases showed a decrease in total leukocyte count to below 2,000/mm3 at the time of induction therapy, but this was transient in all cases. No significant difference in count was noted between two arms at the time of maintenance therapy. However, many cases in Arm T showed decreased total leukocyte count and hemoglobin content, and thrombocytopenia. These results suggest that combination therapy including THP conducted as maintenance therapy after induction is useful in the prolongation of survival time in patients with advanced or recurrent breast cancer.

Topics: Adult; Alopecia; Anorexia; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Floxuridine; Humans; Japan; Middle Aged; Nausea; Neoplasm Recurrence, Local; Survival Analysis; Vomiting

Forty patients with bladder cancer who underwent radiotherapy with angiotensin II, a hypertensor, and two cycles of arterial infusion of anticancer chemotherapies, including cisplatin 100 mg/body, were randomly assigned to a granisetron group and a non-granisetron group for comparative study of its prophylactic effect on nausea, vomiting and anorexia. Granisetron proved significantly effective in preventing nausea, as 75% of granisetron-administered patients experienced either only slight nausea or none at all, against only 22.5% in the non-granisetron group. The number of vomiting episodes was zero during the three-day observation period in 28 out of 40 (70%) granisetron-administered patients compared with 6 patients (15%) in the non-granisetron group. A significant difference in prophylactic effect on anorexia was demonstrated between the granisetron and non-granisetron group, indicating that control of alimentary symptoms such as nausea and vomiting influences the severity of anorexia. As to the safety, nausea was lengthened and deteriorated in one patients. Though the physician in charge judged it to be an adverse event too minor to question the safety of granisetron. Thus, granisetron proved to be highly effective and safe in preventing nausea, vomiting and anorexia in patients under concomitant administration of radiotherapy with hypertensor and arterial infusion of anticancer chemotherapies.

Topics: Aged; Angiotensin II; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Blood Pressure; Child; Cisplatin; Doxorubicin; Female; Granisetron; Humans; Infusions, Intra-Arterial; Methylprednisolone; Nausea; Tegafur; Urinary Bladder Neoplasms; Vomiting

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

In a phase II study, 77 patients with metastatic breast cancer were treated with pirarubicin, 70 mg/m2 iv every 3 weeks. Most of them had received prior hormonal (n = 39) and/or chemotherapeutic drug treatment for advanced disease, including anthracycline-containing regimens in 17. After a median of 5.5 treatment cycles (range 1-14), objective tumor response was seen in 22/71 (31%) evaluable patients (4CR, 18 PR). Stable disease occurred in 34 (48%) patients, whereas the tumor progressed in 15 (21%). Significant hematologic toxicity (WHO grade III-IV) requiring interval and/or dose adjustments was observed in 41 (58%) patients. Other treatment-related side effects were generally mild, and included alopecia in 52 (73%), nausea and/or emesis in 50 (70%), and stomatitis and diarrhea in 3 patients each. There was no treatment-related death, nor was there any evidence of cardiac toxicity thus far. In summary, the early results of this trial suggest that pirarubicin is an active and rather well tolerated drug in pretreated patients with advanced breast cancer.

Topics: Adult; Aged; Alopecia; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Menopause; Middle Aged; Nausea; Vomiting

A phase II study of THP was performed in patients with advanced gastrointestinal cancer. The dose schedule was 25 to 40 mg/m2 i.v./cycle repeated every 3 to 4 weeks. One partial (PR) and one minor response (MR) were achieved in 16 evaluable patients with stomach cancer. A case of PR had previously been shown to be resistant to doxorubicin and a case of MR resistant to aclarubicin, respectively. No objective responses were observed in 19 evaluable patients with other tumor sites in the gastrointestinal tract. Forty-eight patients were evaluable for toxic effects. Leukopenia (less than 4 X 10(3)/mm3) occurred in 54% of the patients and was dose-limiting. Thrombocytopenia (less than 10 X 10(4)/mm3) was less frequently observed (13%) than leukopenia. However, no cumulative marrow suppression was observed in repeated courses of the therapy. Non-hematologic toxic effects consisted of gastrointestinal disturbances (23%), hair loss (10%), general malaise (8%), fever (6%), ECG changes (4%) and hepatic dysfunction (2%). Further trials with a high dose schedule (40 mg/m2, q 3-4 weeks) in good-risk patients are necessary to validate the antitumor activity of THP against advanced gastrointestinal cancer.

Topics: Adult; Aged; Alopecia; Anorexia; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Vomiting

The therapeutic effects of 4'-Epi-Adriamycin (Epi-ADR), THP-Adriamycin (THP-ADR) and Mitoxantrone on 30 patients with advanced and recurrent breast cancer were analyzed. Responders for Epi-ADR, THP-ADR and Mitoxantrone were 5/18, 3/8 and 2/8 respectively. Leukocytopenia less than 3000 was observed in 7/12 for Epi-ADR, 8/8 for THP-ADR and 7/8 for Mitoxantrone. Thrombocytopenia was found in 2 cases treated with Epi-ADR. Gastrointestinal disorders were observed in patients treated with Epi-ADR extensively with THP-ADR moderately and with Mitoxantrone slightly. Marked alopecia was remarkably seen in the patients treated with Epi-ADR, but it was only slight in those treated with THP-ADR and Mitoxantrone. No cardiotoxicity was recorded in any of the patients.

Topics: Adult; Aged; Alopecia; Anthraquinones; Breast Neoplasms; Doxorubicin; Epirubicin; Female; Humans; Middle Aged; Mitoxantrone; Nausea; Neoplasm Recurrence, Local; Vomiting