pirarubicin and Nausea

We previously described the effectiveness of the THP-COP regimen comprising cyclophosphamide, pirarubicin (tetrahydropyranyl adriamycin; THP), vincristine and prednisolone in patients with diffuse large B-cell lymphoma (DLBCL). The anthracycline drug THP was apparently less cardiotoxic than doxorubicin. However, that study was completed before rituximab was introduced into clinical practice. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) against DLBCL.. Six to 8 courses of the regimen were administered every 2 weeks in 48 patients who were younger than 70 years.. The complete remission rate was 92%, the 3-year overall survival rate was 83% and 3-year progression free survival rate was 74%. No deaths were associated with the treatment regimen.. We conclude that R-THP-COP regimen is very effective against DLBCL. The results of our study urge randomized trials of R-CHOP and R-THP-COP among patients with CD20+ DLBCL.

Topics: Aged; Anemia; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Nausea; Neutropenia; Prednisolone; Rituximab; Survival Analysis; Treatment Outcome; Vincristine

Chemotherapy regimen containing anthracyclines has been used as the standard treatment for acute myeloid leukemia (AML). This study was to compare the efficacy and toxicity of the chemotherapy regimen containing perarubicin (THP) with that containing mitoxantrone (MIT) for young patients with newly diagnosed AML.. A total of 129 patients with newly diagnosed AML, aged 16 to 60 years olds, were assigned for induction chemotherapy containing one to two courses with standard-dose cytarabine (Ara-C) and an anthracycline antibiotic, THP or MIT. When complete remission was achieved after induction therapy, the patients received two courses of consolidation therapy identical to the induction regimen. From then, the patients were alternately given four courses of consolidation therapy consisting of Ara-C/THP or Ara-C/MIT every three weeks. Maintenance treatment continued for three years when patients were in continuous complete remission (CCR).. Twenty-six out of 42 patients (61.90%) receiving THP therapy, and 48 out of 73 patients (65.75%) treated by MIT achieved CR (P>0.05). Nine (34.61%) and 11 (22.92%) out of CR patients treated by THP and MIT, respectively, relapsed within one year (P=0.28). Moreover, the incidences of toxicities, such as infection, nausea/vomiting and cardiac events, were similar in these two groups (P>0.05) except for alopecie, which was 26.19% in the THP group compared to 42.47% in the MIT group (P<0.01).. Regimen containing THP plus Ara-C can be used for young adults with newly diagnosed AML for remission induction, but it is not superior to the regimen with MIT. Consolidation chemotherapy with THP or MIT is feasible for young adults with AML after CR.

Topics: Adolescent; Adult; Agranulocytosis; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Nausea; Recurrence; Remission Induction; Young Adult

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Liver; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Vomiting, Anticipatory

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 total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Nausea

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

Clinical study suggests that 72-hour continuous infusion (CIV) of MAID regimen is more effective and achieves longer time of no progression than ADR-based two-drug regimen in advanced soft tissue sarcoma (ASTS) treatment, but has no improvement on the long-term survival. Because of the severe grade 3/4 toxicities as well as treatment-related deaths, the regimen has not been widely applied in ASTS. This study was to investigate the efficacy and toxicity of the modified MAID regimen in ASTS treatment.. In the modified regimen, adriamycin (ADR) was substituted with tetrahydropyranyl adriamycin (THP-ADR) and the application of ifosfamide (IFO) was modified. All enrolled patients received chemotherapy (IFO 2,000 mg . m(-2), 4h, day 1-3; mesna 1,200 mg . m(-2) at 0, 4 and 8 hours of IFO infusion, day 1-3; THP-ADR 20 mg . m-2 and dacarbazine (DTIC) 333.3 mg . m(-2) were mixed in the same bag or pump, CIV for 3 days). The therapy was repeated every 3 weeks for at least 2 cycles before evaluating the effects and toxicities. The patients received follow-up every 2 months after completing 2 cycles until the study was finished. Life table was used to calculate long-term survival rates and time to progression.. Fifty-four cases of evaluable patients had completed at least 2 cycles of modified MAID chemotherapy. The overall response rate was 42.59%. The toxicities were mild. Grade 3/4 neutropenia and thrombocytopenia were 25.93% and 16.17%, respectively. Neutropenia fever was 11.11%. There were no other toxicities, such as hepatic and renal toxicities; no central nervous system toxicity and treatment-related deaths. During 2 year follow-up, time to progression was 7 months, 1- and 2- year survival rates were 61.11% and 36.36%, respectively.. Modified MAID regimen simplifies the application of treatment procedure compared with original regimen, which three drugs have to be CIV simultaneously. Moreover the modified MAID regimen has better survival rates in ASTS, with milder toxicity and better tolerance.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Fibrosarcoma; Follow-Up Studies; Humans; Ifosfamide; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Remission Induction; Rhabdomyosarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms; Survival Rate; Thrombocytopenia; Young Adult

The therapeutic efficacy of weekly coadministration of paclitaxel (TXL) and pirarubicin (THP) on docetaxel (TXT)- and epirubicin-resistant recurrent breast cancer, adverse reactions caused by this therapy, and the possibility of ambulatory treatment using it were evaluated. The present study was conducted in 11 patients with recurrent breast cancer with pretreatment with CEF and TXT. The site of recurrence was the lung in 9 patients, lymphnodes in 2, bones in 1, liver in 1 and local foci in 1. One cycle consisted of 20 mg/m2 of THP followed by 80 mg/m2 of TXL 4 h later, repeated three times every other week. Three to six cycles were conducted in each patient. An anti-emetic drug was administered before administration of THP as short premedication. Dexamethasone (16 mg; i.v.) and d-chlorpheniramine maleate (12 mg; p.o.) were administered 1 h before administration of TXL and ranitidine (100 mg; i.v.) was administered 30 min before administration of TXL. Ubidecarenone (30 mg/day; p.o.) was administered for 3 days. The response rate was 27.3% with a rating of PR in 3 patients, NC in 6, and PD in 2. Adverse reactions observed included transient facial hot flushes, alopecia grade 1 or milder grade 1 symptoms, and peripheral nerve damage. No adverse reactions such as myocardial disorders or congestive heart failure were noted. Grade 3 and grade 2 neutropenia occurred in 1 and 6 patients, respectively, and 4 patients were admitted for treatment of this. In conclusion, the short premedication was useful, and this was thought to make it possible to conduct ambulatory treatment with TXL + THP in some patients. The response rate of 27.3%, however, was not satisfactory. It will be necessary to clarify the characteristics of this therapy by administering it to a wider spectrum of patients.

Topics: Adult; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Paclitaxel

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

Thirty-five non-pretreated patients (29 male, six female) with malignant pleural mesothelioma, median age of 68.5 years (range, 29 to 78 years) and a median performance status of 80% (range, 60% to 100%) were treated with 70 mg/m2 Pirarubicin. The treatment was repeated every 3 to 4 weeks (median duration per cycle, 23 days) up to progression or severe toxicity. The median cumulative dose given was 294 mg/m2, or 4.5 cycles. All patients were evaluable regarding response. Three partial remissions were achieved, leading to a remission rate of 8.6%. The median duration of remission was 6 months. Five patients achieved minor response, and a further 14 patients were stable under treatment with Pirarubicin. The median survival time was 10.5 months. Leukocytopenia was the main dose-limiting factor and 20% of the patients experienced World Health Organization (WHO) Grades III and IV. Anemia and thrombocytopenia were mild. Nausea and vomiting, WHO Grades I and II, were observed in 46% of all patients. Alopecia, Grades I and II, was seen in 47% and Grade III in 6%. No signs of cardiac dysfunction were detectable, except for cardiac arrhythmia in four patients (11%). Pirarubicin is an active drug in the treatment of pleural mesothelioma with fewer severe side effects than doxorubicin.

Topics: Adult; Aged; Alopecia; Arrhythmias, Cardiac; Doxorubicin; Drug Evaluation; Female; Humans; Leukopenia; Male; Mesothelioma; Middle Aged; Nausea; Pleural Neoplasms; Remission Induction; Survival Rate

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 (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

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