pirarubicin and Anorexia

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

A multi-institutional collaborative phase II study of (2"R)-4-O-tetrahydropyranyladriamycin (THP) was performed by intravenous administration to patients with advanced or recurrent gastric cancer. The administration schedules were (1) 40-60 mg/body every 3 or 4 weeks and (2) 20-40 mg/body once a week. Of 58 registered patients, 49 cases were eligible and 37 cases were evaluable for response. The therapeutic results were 1 CR, 4 PR, 14 NC and 18 PD. The response rate of the evaluable cases was 13.5%. The side effects were mainly bone marrow suppression and digestive symptoms. In particular, the frequency of leukopenia was a high 75.5%, while there was a decrease in hemoglobin in 38.8% and anorexia in 30.6%. The frequency and severity of alopecia, which is a known problem with anthracyclines, were slight, and no abnormal electrocardiograms were observed.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Bone Marrow; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Stomach Neoplasms

A comparative study of two combination chemotherapy regimens including (2'' R)-4'-O-Tetrahydropyranyladriamycin (THP) or Adriamycin (ADR) was performed to evaluate its efficacy and safety in advanced and recurrent breast cancer. In this study 64 patients were evaluated, and the response rate was 35.1% (13 of 37 patients) in group A (combination chemotherapy of THP, 5-Fluorouracil and cyclophosphamide), and 29.6% (8 of 27 patients) in group B (ADR, 5-Fluorouracil and cyclophosphamide). There was no statistically significant difference between the response rates of the two groups. As for safety, that of group A was significantly superior to group B for alopecia while that of group A tended to be lower than group B for anorexia. From the above results, THP in combination with cyclophosphamide and 5-Fluorouracil is comparable to ADR in efficacy and can be regarded as having better safety than ADR for the treatment of breast cancer.

Topics: Anorexia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Humans; Middle Aged; Nausea; Neoplasm Recurrence, Local; Random Allocation

Pirarubicin, a new antineoplastic antibiotic of anthracycline derivative, was injected into the pleural cavity in 15 patients with malignant pleural effusion. The dose of pirarubicin was 40 mg or 80 mg/body. All 15 patients were evaluable for both efficacy and toxicity. Since one evaluable patient received two courses of intrapleural administration of pirarubicin, we evaluated a total of 16 courses. Overall response rate was 81.3% with 7 CR cases, 6 PR cases and 3 NR cases. As toxicities, transient elevation of fever was observed in 81.3%, chest pain in 37.5%, appetite loss in 18.8%, nausea in 12.5% and bone marrow suppression in 6.3% of 16 courses, but no alopecia was observed. Between 40 mg group (n = 8) and 80 mg group (n = 8), no significant difference was observed in response rate, response duration, survival duration or toxicities except for fever. Fever over 38 degrees C was observed in all (100%) the 80 mg group, which was significantly higher than 50% in the 40 mg group. Response duration in cases with fever over 38 degrees C (n = 12) was significantly longer than in cases with maximum fever under 38 degrees C (n = 4). Intrapleural administration of pirarubicin was considered to be effective for the treatment of malignant pleural effusion without severe toxicities.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Carcinoma, Small Cell; Chest Pain; Doxorubicin; Female; Fever; Humans; Infusions, Parenteral; Lung Neoplasms; Middle Aged; Pleural Effusion, Malignant; Stomach Neoplasms; Survival Rate

A Phase II clinical trial of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was performed in 137 patients with urological malignancies. Out of them, 111 patients were evaluated for tumor responses and 125 patients were evaluated for adverse effects. In cases of intravenous administration, overall response rate was 18.5% (22.2% for bladder cancer, 30.0% for tumors of the renal pelvis and ureter, and 6.7% for prostatic cancer). In the case of intra-arterial administration, overall response rate was 42.9% (50.0% for bladder cancer). For 50 patients with superficial bladder cancer intravesical chemotherapy with THP was performed. Sixteen patients showed complete disappearance of the tumor, 2 patients showed more than 90% tumor regression and 12 patients showed more than 50% tumor regression, respectively. Overall response rate was 60%. Cardiotoxicity was minimal. Alopecia was noted in a total of 16 patients, but this was minimal. Leukocytopenia was the major adverse effect among patients undergoing systemic THP administration. In conclusion, THP was most effective against transitional cell carcinoma of the urinary tract.

Topics: Adult; Aged; Alopecia; Anorexia; Carcinoma, Transitional Cell; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Kidney Neoplasms; Leukopenia; Male; Middle Aged; Urinary Bladder Neoplasms; Urologic Neoplasms

A Phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was conducted in 162 patients with various hematological malignancies in a multi-institutional cooperative study. THP was given intravenously at a dose of either 10-30 mg/body for 3-5 consecutive days or 40-60 mg/body at 3-week intervals. Of 22 patients with AML, complete remission (CR) was observed in 2 patients and partial remission (PR) in 2. Of 18 patients with ALL, CR was observed in 5 and PR in 3. Of 68 patients with NHL, CR was observed in 11 and PR in 22. Of 8 patients with HD, CR was observed in 4 and PR in 2. One CML case showed CR and one ATL case showed PR. PR was noted in one of 2 patients with mycosis fungoides. Overall remission rate was 43.1% (CR 23 cases and PR 33 cases). The predominant toxicity was myelosuppression. Leukopenia (less than 4,000/mm3) was noted in 67 (77.6%) and thrombocytopenia (less than 10 X 10(4)/mm3) in 24 (27.0%). Nausea/vomiting and anorexia were common, and were observed in 61 (43.3%) and 65 (46.1%) cases, respectively. Hair loss and cardiotoxicity were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for various hematological malignancies including acute leukemia and malignant lymphoma.

Topics: Acute Disease; Adolescent; Adult; Aged; Anorexia; Antineoplastic Agents; Child; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia; Leukopenia; Lymphoma; Male; Middle Aged

In a phase II study of THP, fifty-six patients with advanced or recurrent breast cancer were evaluated, and a response rate of 23.2% including 1.8% with complete response and 21.4% with partial response, was obtained. Response rates of THP varied according to the location of metastasis and the highest rate was shown to be 38.5% in patients with soft tissue metastasis. The median dose for inducing response was 100 mg with a range from 60 mg to 160 mg. Toxicities such as leukopenia and gastrointestinal disorders were observed during THP treatment. The favorable response to THP was close to that of adriamycin, but it was noteworthy that a lower frequency of alopecia occurred.

Topics: Adult; Aged; Anorexia; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Middle Aged; Nausea; Neoplasm Recurrence, Local

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

A Phase II Study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with various solid tumors was carried out by 44 cooperative study institutions. Seven hundred fifty-six patients administered the drug intravenously were entered into this study. Of these, 499 patients were evaluated for objective responses. THP was given mainly at a dose of 40 to 60 mg/body every 3 to 4 weeks or 20 to 30 mg/body once a week. Response rates were 18.8% for head and neck cancer, 13.1% for stomach cancer, 21.4% for breast cancer, 22.2% for bladder cancer, 30% for renal pelvic and urinary tract tumor, 26.8% for ovarian cancer and 24.2% for uterine cancer. Overall response rate was 15.4% including 10 complete responses and 67 partial responses. Adverse reactions were similar to those previously reported in the phase I study, including gastrointestinal toxicities and myelosuppression. Alopecia and stomatitis, which are major side effects of other anthracyclines, were rather mild. Incidence of ECG changes was 2.8% and no congestive heart failure was observed.

Topics: Adult; Aged; Alopecia; Anorexia; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukopenia; Male; Middle Aged; Nausea; Neoplasms

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Topics: Aged; Anorexia; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukopenia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Nausea; Neoplasms; Stomach Neoplasms; Thrombocytopenia

A phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP) was performed on 37 patients with gastrointestinal cancer in 6 co-operative study institutions. Twenty-five patients out of 37 were evaluable for response according to the Koyama-Saito's criteria. THP was administered weekly at doses of 10 to 30 mg/body or every 3 to 4 weeks at doses of 40 to 60 mg/body intravenously. Of the 14 patients with gastric cancer, we obtained one complete response and 3 partial responses (response rate 28.6%), and of the 6 patients with rectal cancer, we obtained one partial response (16.7%). Leukopenia of less than 3 X 10(3)/mm3 and erythrocytopenia of less than 300 X 10(4)/mm3 were seen in 48% and 26% of cases. Neither cardiotoxicity nor hair loss were seen. These results suggest that THP is useful in the treatment of patients with gastrointestinal cancer.

Topics: Adult; Anorexia; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukopenia; Male; Middle Aged; Nausea; Rectal Neoplasms; Stomach Neoplasms

Of 3 patients with adult ALL and 23 patients with NHL treated with intravenous administration of 10 mg/M2 of THP for 5 consecutive days, complete remission was observed in 3 patients and partial remission in 14. The antitumor spectrum of THP seemed to be similar to that of Adriamycin from evidence that THP was effective in patients with NHL of diffuse large and mixed cell type. Neither cardiotoxicity nor alopecia was noticed. Anorexia, nausea or vomiting was mild but granulocytopenia and thrombocytopenia were severe in the patients with ALL and leukemic type NHL. Further studies are required for determining cross resistance to other anthracyclines and an optimal dose schedule.

Topics: Adult; Aged; Anorexia; Antibiotics, Antineoplastic; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Leukopenia; Lymphoma; Male; Middle Aged; Naphthacenes; Nausea; Stomatitis; Thrombocytopenia