pirarubicin and Lymphoma

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials, Phase I as Topic; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphoma; Mesothelioma

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Combined Modality Therapy; Doxorubicin; Female; Humans; Immunotherapy; Lymphoma; Male; Methotrexate; Middle Aged; Pilot Projects; Procarbazine; Rituximab

We report the efficacy of salvage therapy with a modified ProMACE-MOPP combined with radiation in patients with primary central nervous system lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristin, and methotrexate (MTX: 500 mg/m(2)) administered in 21-day cycles. Patients received 20 Gy of whole-brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every four months for two years. Nine patients with CNS relapse were retreated with additional cycles of the ProMACE-MOPP hybrid regimen with a 90% objective response rate. Median complete response (CR) duration was 13.2 months and median survival time (MST) for the nine patients treated after initial relapse was 30 months. One of 17 patients (5.8%) who had less than 20 Gy of whole brain irradiation developed dementia. In contrast, six of seven (85.7%) patients who had more than 30 Gy of whole brain radiotherapy became demented. Maintaining a moderate dose of MTX, while adding chemotherapeutic agents and 20 Gy of whole brain radiation therapy, improved disease control and overall survival and lowered the incidence of delayed neurologic toxicity in patients with PCNSL. Additional treatment with a ProMACE-MOPP hybrid regimen is still effective for relapsed disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Lymphoma; Male; Mechlorethamine; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Prednisone; Procarbazine; Retrospective Studies; Salvage Therapy; Survival Analysis; Vincristine

To determine the effect of a chemotherapy regimen containing pirarubicin, a multicenter clinical trial was performed in naive patients > or = 65 years with malignant lymphoma, between January 1990 and December 1992. The total number of patients was 37 (median age 74.2 years). One of three different types of chemotherapy regimens, which was administered every 3 to 5 weeks, was chosen for each patient at random. Regimen A (THP-COP) included pirarubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1), vincristine (1 mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5), regimen B, modified "CHOP", included doxorubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1) vincristine (1 mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5); regimen C (THP-COPE) included etoposide (80 mg/m2; day 1) in addition to regimen A. The complete response (CR) rate was 60.0%, 45.5% and 62.5% with regimen A, B and C. The partial response (PR) rate with regimen A was 20.0%, 18.2% with B and 25.0% with C. The 50% survival period with regimen A was more than 1,000 days, with C 643 days but it was only 365 days with B. The adverse effects related to these treatments occurred more frequently in regimen B than A and C showing a statistically significant difference. We concluded that chemotherapy regimens containing pirarubicin are useful and safe for the elderly patients with malignant lymphoma.

Topics: Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Double-Blind Method; Doxorubicin; Female; Follow-Up Studies; Humans; Lymphoma; Male; Prednisolone; Survival Rate; Treatment Outcome; Vincristine

(2'' R)-4'-O-Tetrahydropyranyl Adriamycin (THP) is a new antitumor agent discovered among series of similar anthracycline compound synthesized by Umezawa et al. Phase I study revealed dose limiting factor of leukopenia with upper GI toxicity. Alopecia, cardiac failure and transient hepatic failure were extremely mild. Definite responses were demonstrated in acute leukemia, lymphoma, ovarian carcinoma, head and neck carcinoma, breast carcinoma and GU carcinoma. Pharmacokinetic studies revealed rapid cell uptake and outputs in bile (20%) and urine (8%) in 24 hours. Transfer to third spaces were poor but definite. In vivo a part of THP was converted to ADM in the liver, but not in other tissues including tumors. THP would be an extremely interesting compound, because of comparable spectrum of responses to various tumors with extremely low toxicity compared with other anthracycline compounds.

Topics: Acute Disease; Clinical Trials as Topic; Doxorubicin; Gastrointestinal Diseases; Humans; Leukemia; Lymphoma; Neoplasms

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Electrocardiography; Female; Heart; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Naphthacenes

Topics: Aclarubicin; Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Clinical Trials as Topic; Cytarabine; Doxorubicin; Drug Evaluation; Humans; Infusions, Parenteral; Leukemia, Myeloid, Acute; Lymphoma; Middle Aged; Naphthacenes

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Doxorubicin; Drug Evaluation; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged

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

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

To investigate the detailed acute cardiotoxicity of the anthracycline antibiotics, adriamycin (ADM) and a tetrahydropyranyl derivative (THP-ADM), Holter ECG was recorded and some of the electrocardiographic parameters were analyzed. The basic rhythm was sinus rhythm in many cases except only one case which developed intermittent atrial fibrillation after the administration of ADM. No effect on the specialized conduction system was observed in either ADM or TH-PADM. In relation to the supraventricular premature beat, no increase of the pre-existing supraventricular extrasystole and fresh appearance of the supraventricular extrasystole were observed after the administration of these drugs. On the other hand, the ventricular premature beat was tended to increase after ADM administration, and the mode of appearance of the ventricular extrasystole was very dangerous and life-threatening. For example, short-run type and R on T type ventricular extrasystole were recorded. THP-ADM induced no significant increase of the ventricular extrasystole. The developed ST-T changes were seen after the administration of these drugs, but the patients complained neither the symptoms of heart failure nor stenocardia. In conclusion. THP-ADM had less cardiotoxicity than ADM.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Breast Neoplasms; Cardiac Complexes, Premature; Doxorubicin; Electrocardiography; Female; Heart; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; 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

A phase II clinical trial of a new anthracycline, 4'-O-tetrahydropyranyladriamycin (THP-ADM), was performed in thirty-one patients with advanced malignant tumors refractory to standard chemotherapies. The dosage of THP-ADM was 40 mg/m2 by iv bolus injection repeated every 3 weeks. Of 3 evaluable patients with non-Hodgkin's lymphoma, one achieved partial remission. A minor response was noted in one out of 7 patients with gastric cancer and one out of 5 patients with ovarian cancer. Leukopenia less than 4 X 10(3)/cmm and thrombocytopenia less than 100 X 10(3)/cmm were seen in 81% and 19% of cases, respectively. Mild gastrointestinal toxicities including nausea and vomiting and anorexia were observed in about one third of the patients. Mild hair loss occurred in 2 patients (6%). No ECG abnormalities on clinical sign of cardiotoxicity were seen.

Topics: Aged; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Lymphoma; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Stomach Neoplasms

THP-ADM is a new antitumor antibiotic which belongs to the anthracycline group. This agent was administered to 42 histology proven various malignant disease patients with a schedule of 60-80 mg per body (40-55 mg per m2) iv bolus, every three weeks. THP-ADM administration revealed mild upper GI toxicity (vomiting 19%, stomatitis 21%) and leukopenia (less than 2,000 per mm3) in 80% and thrombocytopenia (less than 60,000 per mm3) in 38% with good rebound. There was no signs or symptoms of cardiac failure including the patient who had received 740 mg per body (500 mg per m2). Definite response (CR, PR) was observed in ovarian carcinoma 4/11, cervix carcinoma 2/7, breast carcinoma 1/6, malignant lymphoma 5/5 and mesothelioma 1/2. Furthermore, some response (MR) was observed in lung metastasis from endometrial carcinoma 2/4, and stomach carcinoma 1/3. The above indicated usefulness of this agent and further study should be continued, especially a controlled study with adriamycin.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Doxorubicin; Drug Evaluation; Female; Humans; Lymphoma; Male; Mesothelioma; Middle Aged; Ovarian Neoplasms; Sarcoma; Stomach Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms