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P Klimo

Publications and source records attributed to P Klimo.

At least 19 recordsLinked to original sources
PubMed1997

Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group.

PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.

Actuarial Analysis↗
PubMed1997

Late relapse in patients with diffuse large-cell lymphoma treated with MACOP-B.

PURPOSE: To examine the clinical course of patients who experienced a late relapse after initial curative chemotherapy for advanced-stage diffuse large-cell lymphoma. PATIENTS AND METHODS: Between April 1981 and June 1986, 127 patients with de novo advanced-stage diffuse large-cell lymphoma were treated with a 12-week chemotherapy program (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]). The overall survival rate at 10 years is 52%. One hundred six patients (83%) entered a complete remission (CR) and 43 of them relapsed. With a median follow-up duration of 146 months, 26 patients relapsed early and 17 relapsed late, ie, after a continuous CR (cCR) of greater than 24 months. All late relapses occurred in patients with B-cell lymphoma. RESULTS: After 24 months from diagnosis, the rate of late relapse averaged 2.2% per year and reached a projected 22% actuarial risk of late relapse after 10 years. The median time to late relapse was 69 months (range, 38 to 141). Ten patients relapsed with aggressive histologic subtypes and were treated with curative intent using anthracycline-based chemotherapy. Four remain in second CR, one is alive with disease, and five died of disease or while on treatment. The 6-year overall survival rate from the time of relapse (SFR) for these 10 patients is 42%. Six patients relapsed with low-grade follicular lymphoma. These patients received various treatments intended to control, but not necessarily cure disease. One is in second CR, one is alive with disease, and four died of disease or while on treatment. The 6-year overall SFR rate for these six patients is 40%. bcl-2 translocation and Bcl-2 protein expression at diagnosis did not predict for the type of late relapse. One patient did not undergo repeat biopsy at relapse and died 9 months later despite aggressive therapy. CONCLUSION: Curative therapy should be attempted in patients who relapse late with aggressive-histology lymphoma and those who relapse with follicular histology may benefit from palliative treatment. The behavior of late-relapse lymphoma is similar to de novo lymphoma, with outcome dictated by the histologic subtype at relapse.

Adult↗
PubMed1997

Phase II trial of gemcitabine and weekly cisplatin for advanced non-small cell lung cancer.

Single-agent gemcitabine, when given in doses of > or = 1,250 mg/m2 weekly x 3 with a 1-week break, induces responses in approximately 20% of untreated patients with non-small cell lung cancer. This phase II study was undertaken to determine the efficacy of weekly administration of gemcitabine 1,500 mg/m2 combined with cisplatin 30 mg/m2 x 3 with a rest period of 1 week. Patients younger than 75 years were eligible if they had stage III/IV non-small cell lung cancer, a life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes no more than three times the upper limit of normal, and serum creatinine < or = 130 micromol/L. There were 22 men and 18 women, with a median age of 60 years; 35 had a performance status of 0 or 1. Pathology included adenocarcinoma in 22 patients, squamous cell carcinoma in nine, large cell carcinoma in seven, and mixed non-small cell lung cancer in two. Six patients had stage III and 34 had stage IV tumors. Of the 39 patients eligible for response evaluation, partial remission was seen in 10, for an overall response rate of 26% (95% confidence interval, 12% to 41%). The median duration of response was 19 weeks (range, 7 to 32+ weeks). Grade 3/4 anemia was seen in 11 patients, and 21 patients required red blood cell transfusions. Grade 3/4 neutropenia occurred in 22 patients and grade 3/4 thrombocytopenia in 21 patients. One patient experienced febrile neutropenia Hematologic toxicity, particularly thrombocytopenia, was cumulative over time. Nonhematologic toxicity was modest, but one patient stopped therapy because of a grade 2 skin rash and one stopped because of a grade 4 pulmonary toxicity, both of which were thought to be related to gemcitabine. The modest activity of weekly gemcitabine and weekly cisplatin seen in this trial does not suggest in vivo synergy for these two agents as administered using this schedule and these doses.

Adult↗
PubMed1993

In search of an optimal regimen for elderly patients with advanced-stage diffuse large-cell lymphoma: results of a phase II study of P/DOCE chemotherapy.

PURPOSE: The results of a prospective, phase II trial of an 8-week treatment program consisting of epirubicin or doxorubicin, vincristine, cyclophosphamide, etoposide, and prednisone (P/DOCE) for elderly patients with advanced large-cell lymphoma are reported and compared with previous phase II studies conducted in similar patients at the same institution. PATIENTS AND METHODS: Between March 1988 and September 1991, 63 previously untreated patients aged 65 to 85 years (median, 75) with advanced-stage diffuse large-cell lymphoma, defined as Ann Arbor stage III or IV or stage I or II with B symptoms or bulky disease, were enrolled on a brief, 8-week protocol consisting of five outpatient chemotherapy treatments. RESULTS: The complete response (CR) rate was 62%. The treatment-related mortality rate was 8%, the actuarial 4-year failure-free survival (FFS) rate was 41%, and the overall survival (OS) rate was 45%. These results were compared with two earlier, 12-week protocols, low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOB-B) and etoposide, doxorubicin, bleomycin, and prednisone (VABE), performed at the same center. There was no difference in outcome among the three regimens. If all 133 patients treated on any one of these three specially designed regimen for elderly patients are combined, the projected 5-year OS rate is 38%. CONCLUSION: The 8-week P/DOCE chemotherapy regimen is equal in efficacy and similar in toxicity to 3 months of chemotherapy administered on a weekly schedule and similar to the results reported in the literature for longer, anthracycline-based chemotherapy treatments. There does not appear to be any improvement in outcome from more protracted treatment programs compared with the 8-week P/DOCE protocol.

Aged↗
PubMed1991

The evolving role of etoposide in the management of lymphomas and Hodgkin's disease.

Etoposide, a derivative of epipodophyllotoxin, is one of the most important new drugs that was introduced into the management of the malignant lymphomas during the past decade. A growing number of specific protocols include this useful agent in the management of malignant lymphoma, both at the time of primary treatment and at relapse. The broad activity of etoposide across several histologic subtypes of malignant lymphoma and Hodgkin's disease indicates a potential that is only now being fully exploited. Used according to optimal doses and schedules, etoposide has single-agent activity that rivals earlier drugs such as the alkylating agents and doxorubicin. Functioning as a protein synthesis and topoisomerase II inhibitor, it offers the potential for non-cross-resistant cytotoxicity. After a brief comment on the single-agent activity of etoposide, this report will focus on the integration of etoposide into multiagent protocols used in the primary treatment of malignant lymphoma and Hodgkin's disease. The specific findings from protocols such as prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide-cytarabine, bleomycin, vincristine, and methotrexate (Pro-MACE-CytaBOM) (US National Cancer Institute [NCI]) and etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) (Vancouver) for the primary treatment of malignant lymphoma, and vinblastine, etoposide, cyclophosphamide, doxorubicin, bleomycin, vincristine, and prednisone (VECABOP) (Vancouver) for the treatment of previously untreated patients with advanced Hodgkin's disease will be discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

MACOP-B and VACOP-B in diffuse large cell lymphomas and MOPP/ABV in Hodgkin's disease.

Between 1981 and 1986, 126 patients with diffuse large cell lymphoma were treated with MACOP-B (methotrexate/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomy cin). All had advanced-stage lymphoma (Ann Arbor stage III or IV or stage I or II if the tumor mass was greater than 10 cm or B symptoms were present). The complete response (CR) rate was 84% and the toxic death rate was 6%. Actuarial overall survival at 3 years was 67% and at 8 years 62%; the failure-free survival at 8 years was 52%. The follow-up for MACOP-B is 39 to 106 months (median 76) for living patients. A multivariate prognostic factor analysis for this group of patients identified age greater than 60 years. B symptoms, more than one extranodal site of disease, and more than three nodal sites of disease as the four significant prognostic variables. From June 1986, 108 patients were enrolled on a modification of MACOP-B called VACOP-B (etoposide/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin ). Their CR rate was 81%, and the toxic death rate was lower, at 3%. The 60% overall survival at 3 years is not statistically significantly different from that of MACOP-B. The incidence of moderate or severe mucositis and Cushingoid changes was much lower with VACOP-B. The MOPP/ABV (mechlorethamine/vincristine/procarbazine/prednisone- doxorubicin/bleomycin/vinblastine) hybrid chemotherapy regimen for advanced-stage Hodgkin's disease was standard therapy from April 1981 to June 1988 for untreated patients aged 16 to 65. Advanced stage was defined as stages IIB, IIIB, III2A, IVA, IVB, or stages IIA or IIIA with greater than four splenic nodules or a mediastinal mass greater than one third of the transthoracic diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1991

Prognostic variables in patients with diffuse large-cell lymphoma treated with MACOP-B.

One hundred twenty-six patients with diffuse large-cell lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between April 1981 and June 1986. Univariate and multivariate analyses were performed using overall survival as of September 1989 as the end point. Four independent negative predictors of survival were identified: presence of B symptoms; more than two involved lymph node sites; more than one extranodal site (variables related to tumor burden), and age older than 60, a variable related to the patient's ability to tolerate treatment. Each variable contributed the same relative risk of dying and, accordingly, this simple predictive formula was developed empirically: (4-N) x 30 = the approximate percentage of chance of survival at 5 years. "N" is the number of predictive variables present. The same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed.

Adolescent↗
PubMed1991

Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma.

Elderly patients with advanced-stage diffuse large-cell lymphomas (DLCLs) are either excluded from or under-represented in most clinical trials of combination chemotherapy regimens because they tolerate treatment poorly and usually have a worse outcome. We report two brief weekly chemotherapy regimens designed specifically for elderly patients. Eligible patients were aged 65 to 85 years, had advanced-stage DLCL (diffuse mixed, diffuse large-cleaved or noncleaved, immunoblastic, or diffuse large-cell not otherwise specified). Advanced stage was defined as Ann Arbor stage III or IV or stage I or II with a mass greater than 10 cm or B symptoms. Low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOP-B) accrued 40 patients between March 1983 and September 1985; 65% achieved a complete response (CR), there were two toxic deaths, the actuarial failure-free survival (FFS) is 19%, disease-specific survival (DSS) 30%, and overall survival (OS) 28%, with a maximum follow-up of 6 years. The regimen of etoposide, doxorubicin, vincristine, bleomycin, and prednisone (VABE) accrued 32 patients between July 1985 and June 1987; 63% achieved a CR, there were two toxic deaths, and the actuarial FFS is 34%, DSS 45%, and OS 36%, with a maximum follow-up of 4 years. There is no difference in FFS, DSS, or OS between these two regimens. VABE caused more myelosuppression and infectious complications, although the toxic death rates were similar. We prefer LD-ACOP-B because follow-up is longer and toxicity is less.

Aged↗
PubMed1988

A randomized trial of maintenance versus no maintenance melphalan and prednisone in responding multiple myeloma patients.

In order to assess the role of maintenance melphalan and prednisone (MP) in responding multiple myeloma patients, 185 eligible patients who responded to initial MP with stabilization for at least 4 months were randomized to either stop treatment and resume therapy at relapse or to continue MP until relapse. Time to first relapse was significantly shorter in the no maintenance group (P = 0.0011), however 57% of the no maintenance patients had a second response when MP was restarted and others had minor improvement. The time to final progression on MP, which reflects the duration of disease control by MP, was therefore longer for the no maintenance group (median = 39 months) compared to the maintenance group (median = 31 months) although the observed difference was not statistically significant (P = 0.086). Median survival from start of MP in the maintenance group (46 months) was also not significantly different than the no maintenance group (51 months) (P = 0.587). Multifactor analysis of the randomized patients demonstrated shorter total remission duration and shorter survival in patients who had an initially rapid response to therapy or a lesser reduction in serum M-protein concentration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Testicular lymphoma: improved outcome with early brief chemotherapy.

We investigated the impact of early brief chemotherapy on the natural history of primary testicular lymphoma. We compared the outcome for patients seen before 1980--a group primarily managed with orchiectomy and regional radiation--with those seen from 1980 to 1986--a prospectively and consecutively gathered group who were offered brief chemotherapy in addition to standard orchiectomy and irradiation. The historical and study groups were similar in clinical characteristics. However, the chemotherapy group had a better relapse-free survival, 93% v 50% (P less than .02), and overall survival, 93% v 50% (P less than .02). With a median follow-up of 44 months in the chemotherapy group, it is clear that the use of early, brief chemotherapy strongly alters the natural history of testicular lymphoma by preventing relapses, the large majority of which occur early after regional therapy. We conclude that a program incorporating orchiectomy, early brief chemotherapy, and involved-field radiation therapy confers the following benefits on patients with primary testicular lymphoma: (1) laparotomy is not needed for staging; (2) relapses, including those in the opposite testicle and CNS, are largely prevented; and (3) toxicity can be kept to a modest level acceptable in elderly patients.

Aged↗
PubMed1988

An update on the Vancouver experience in the management of advanced Hodgkin's disease treated with the MOPP/ABV Hybrid program.

Between February 1980 and July 1984, 79 patients with newly diagnosed advanced Hodgkin's disease were treated with a new seven-drug regimen, the mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) MOPP/ABV) Hybrid. The treatment plan allowed for a course of involved-field radiotherapy (RT) (3,500 cGy in 20 fractions) to a single area of residual lymph-node-related abnormalities if still present after six cycles of chemotherapy. Of 76 evaluable patients, 74 (97.5%) achieved complete remission (CR), ten (13%) with assistance of involved-field RT. Only two patients (2.5%) were primary treatment failures. Seven patients (9.5%) relapsed; all relapses occurred in the first 24 months of follow-up. The majority of relapses were males with large mediastinal masses and B symptoms. The actuarial overall survival of all 79 patients with the maximum and median follow-up times of 80 and 53 months, respectively, is 93.5%. The actuarial relapse-free survival for the 74 CRs with the maximum and median follow-up times of 71 and 46 months, respectively, is 90.5%. The treatment tolerance was acceptable; only one patient died from causes directly related to the treatment, and less than 10% of patients required hospitalization for suspected or proven systemic infection. The treatment delivery was excellent, as greater than 75% of the treated patients took greater than 90% of the prescribed treatment; greater than 90% of patients received at least 75% of the calculated doses of drugs. This long-term follow-up report supports our initial impression that the MOPP/ABV Hybrid chemotherapy is an effective and well-tolerated program for patients with advanced Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

MACOP-B chemotherapy for malignant lymphomas and related conditions: 1987 update and additional observations.

Between 1981 and 1986, we treated 179 newly diagnosed patients with advanced-stage malignant lymphoma or related conditions with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B). Experience with 12 different histologic subtypes indicates that MACOP-B is acceptably tolerated and effective for diffuse large cleaved cell, diffuse large noncleaved cell, diffuse mixed large and small cleaved cell, immunoblastic, and discordant lymphomas but not for angioimmunoblastic lymphadenopathy or for diffuse small cleaved cell, follicular large cell, follicular mixed large and small cleaved cell, acquired immune deficiency syndrome (AIDS)-related, unclassifiable, or small noncleaved cell lymphomas. Pooled long-term results for the 126 patients with variants of diffuse large cell lymphoma (cleaved, noncleaved, immunoblastic, and mixed) show an actuarial relapse-free survival of 67% for the 86% of patients who had a complete response and an overall survival for all patients of 65% at 78 months of follow-up. Analysis of toxicity reveals a substantially higher risk of lethal toxicity in patients over 59 years of age. MACOP-B should only be used for patients with one of the diagnoses for which it is effective; meticulous care should be taken to prevent severe toxicity in older patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Ketoconazole versus nystatin as prophylaxis against fungal infection for lymphoma patients receiving chemotherapy.

We evaluated the efficacy and toxicity of ketoconazole versus nystatin antimycotic prophylaxis in a prospective randomized study of 32 patients receiving intensive weekly outpatient combination chemotherapy for non-Hodgkin's lymphoma with crossover to the other drug if failure occurred. Thirteen patients were assigned to nystatin and 19 to ketoconazole. Fungal infections occurred in three patients receiving nystatin (16%) and one patient receiving ketoconazole (8%); one patient refused his assigned drug due to taste intolerance. Including the crossover courses of drug, the failure rate associated with ketoconazole was 6% while that for nystatin was 20% (p = 0.23). We favor ketoconazole as antifungal prophylaxis during antilymphoma chemotherapy because of at least equivalent and possibly superior efficacy, better acceptance by patients, easier administration, and systemic absorption.

Aged↗
PubMed1987

Brief chemotherapy and involved field radiation therapy for limited-stage, histologically aggressive lymphoma.

STUDY OBJECTIVE: To determine the efficacy and toxicity of brief chemotherapy and involved field radiation therapy for treatment of limited-stage, histologically aggressive malignant lymphoma. DESIGN: Single-arm prospective trial. SETTING: Comprehensive cancer treatment center serving the entire population of British Columbia. PATIENTS: Consecutive enrollment of 78 patients ranging in age from 21 to 82 years (median, 64) with limited-stage (no B symptoms, Ann Arbor stage I or II, tumors less than 10 cm in diameter), diffuse large cell, mixed or immunoblastic histologic characteristics of malignant lymphoma seen at our institution between May 1980 and December 1984. All eligible patients were evaluated for response and relapse-free and overall survival. INTERVENTIONS: Chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for three cycles followed by involved field radiation therapy to the original site of disease in a dose equivalent to 3000 cGy in ten fractions. MAIN RESULTS: The complete response rate was 99% (77 of 78 patients). With a median follow-up off treatment of 30 months the actuarial relapse-free survival is 84% and the overall survival is 85%. No deaths due to toxicity occurred. CONCLUSIONS: Brief chemotherapy and involved field radiation therapy is highly successful treatment for patients with limited-stage, histologically aggressive malignant lymphoma. Toxicity of this approach is acceptable, even in the elderly. Staging laparotomy is not needed to select these patients. Future trials should incorporate more effective chemotherapy programs.

Adult↗
PubMed1987

Updated clinical experience with MACOP-B.

This paper summarizes our experience with MACOP-B chemotherapy (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) in 125 patients with advanced stage, diffuse, large cell non-Hodgkin's lymphoma referred to the Cancer Control Agency of British Columbia between April 1981 and June 1986. Complete response (CR) was achieved in 105 patients (84%), partial response (PR) in 18 patients (14.4%) and primary treatment failure occurred in two patients (1.6%). Fifteen of the PRs and both nonresponders succumbed to their disease. Of the 105 CRs, 23 patients (21%) suffered a relapse; 14 of the relapsers eventually died from their lymphoma, five are in second CR, three are receiving further therapy, and one has histologic evidence of asymptomatic, low-grade lymphoma. Three deaths were unrelated to lymphoma. Overall toxicity was acceptable, with only six treatment-related deaths (4.8%). The incidence of nonfatal systemic proven or suspected infections was 10%. Mucocutaneous side effects remain the most frequent toxicity of the MACOP-B protocol. More than half of the 125 patients received at least a portion of MACOP-B from community oncologists. The results of treatment with MACOP-B remain at least comparable to the best reported in the literature, yet they have been achieved with less toxicity, over shorter periods of time, and with diminished socioeconomic impact on patients. However, improvement on these results is necessary both in terms of efficacy and toxicity. A new variant of MACOP-B is now being tested and our preliminary experience has been encouraging.

Adult↗
PubMed1987

MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease.

Seventy-six patients with previously untreated advanced Hodgkin's disease have been treated with the MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vincristine) hybrid program. Ten patients also received involved field radiation to the mediastinum for residual nodal disease after six cycles of chemotherapy. Of the 74 evaluable patients, 71 (96%) had a complete response. The actuarial relapse-free survival for the complete responders after 62 months off treatment is 90% (median follow-up from treatment completion was 35 months; range, 4 to 62 months). Actuarial overall survival for all 76 patients including all causes of death is 95% (median follow-up time from diagnosis was 43 months; range, 4 to 70 months). Toxicity was modest. Only one death occurred during treatment, and toxicity-related hospitalization was necessary for only 8% of patients. Failure analysis indicates that a disproportionate number of treatment failures occurred in the sub-group with B symptoms and a mediastinal mass ratio greater than one third the transthoracic diameter. This updated report confirms the efficacy and safety of the MOPP/ABV hybrid program for advanced Hodgkin's disease, which is now being tested in a prospective, randomized, multicenter trial.

Adolescent↗