pirarubicin and Neutropenia

Pirarubicin tetrahydropyranyl adriamycin (THP-ADR) is an analogue of doxorubicin. This agent exhibits activity against some doxorubicin-resistant cell lines. We performed a phase II study of biweekly THP-COP [50 mg/m(2) pirarubicin, 750 mg/m(2) cyclophosphamide, 1.4 mg/m(2) vincristine (2.0 mg maximum) on day 1, and 100 mg/body predonisolone on days 1-5] in patients with peripheral T-cell lymphoma (PTCL). Seventeen patients with newly diagnosed PTCL were enrolled. Histological diagnoses were of PTCL, not otherwise specified (n = 5), or angioimmunoblastic T-cell lymphoma (n = 12). All diagnostic specimens including those of the historical control group were centrally reviewed by hematological pathologists. All patients received six cycles of biweekly THP-COP. The patient group included 13 male and 4 female patients, with a median age of 62 years. The median follow-up time in surviving patients was 30 months. Overall response rate was 94% with 15 cases of complete remission (88%). The 3-year progression-free survival and overall survival rates were 57% and 75%, respectively. The most frequent adverse events associated with biweekly THP-COP were leukocytopenia (100%), neutropenia (100%), and lymphopenia (100%), followed by alopecia (92%) and anaemia (88%). All of these occurred only transiently, and the patients subsequently recovered. Biweekly THP-COP is a safe and promising therapy for patients with newly diagnosed PTCL. This study is registered in a public database (UMIN000010485).

Topics: Adolescent; Adult; Aged; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Follow-Up Studies; Humans; Leukopenia; Lymphoma, T-Cell, Peripheral; Lymphopenia; Middle Aged; Neutropenia; Prognosis; Survival Analysis; Treatment Outcome; Vincristine; Young Adult

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

The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer.. Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter.. The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months.. The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neutropenia

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.

Topics: Animals; Colorectal Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Liver Neoplasms, Experimental; Neutropenia; Rabbits

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

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

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Mastectomy; Middle Aged; Neutropenia; Pilot Projects; Thrombocytopenia; Treatment Outcome; Vinblastine; Vinorelbine

A 63-year-old Japanese woman who was being treated for liver cirrhosis was diagnosed as having hepatocellular carcinoma in the caudate lobe of the liver. Transcatheter hepatic arterial chemoembolization was performed for this lesion, but severe neutropenia occurred. To restore white blood cell (WBC) counts, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (250 micrograms per day during 10 days, intravenously). Subsequently, WBC counts recovered immediately without side effects. This suggests that rhG-CSF could be useful for the treatment of neutropenia after chemoembolization, even in cirrhotic patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Liver Cirrhosis; Liver Neoplasms; Middle Aged; Neutropenia; Recombinant Proteins