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J M Connors

Publications and source records attributed to J M Connors.

At least 73 records · Page 4Linked 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

Malignant lymphomas in the elderly.

More than half of all lymphomas occur in patients aged 60 years or older. This article reviews the management of low-grade and aggressive histology lymphomas in patients older than age 65. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy is well tolerated in patients who have a good performance status and who have aggressive histology lymphoma, but briefer 8-week regimens appear to offer similar benefits more quickly. Age alone is an adverse prognostic factor for lymphomas, but when possible, patients should be offered effective treatment tailored for their age performance status and intercurrent diseases.

Aged↗
PubMed1994

Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy.

The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16-213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post-BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: "B" symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors.

Adolescent↗
PubMed1994

Identification of risk factors in patients treated for first relapse of Hodgkin's disease.

This review focuses on potential risk factors in patients relapsing with Hodgkin's disease after a first chemotherapy/radiation therapy induced complete remission. This patient group usually presents with highly treatment responsive disease and has become one of the target groups for consideration of salvage high dose chemotherapy with stem cell/autologous marrow support (HDC/ABMT). It is currently not clear to which patients in first relapse this treatment should be offered. The knowledge of certain risk factors could be of great help in assessing such patients. A first group of risk factors are those assessable at initial diagnosis: sex, age, histology, Ann Arbor stage, tumour bulk and some laboratory parameters. A second group of risk factors are those present at the time of relapse: time to relapse, extent of disease at relapse, B-symptoms and performance status, extra nodal lesions at relapse or a relapse within an irradiated field. Age below 50 years seems to exert a small influence on outcome but becomes a major problem above that. There is a small number of characteristics such as the time from the end of initial treatment to relapse or B-symptoms at relapse which seem to be the most prominent factors predicting for freedom from second failure (FF2F). Patients who relapse more than one year after finishing primary chemotherapy and who are free of B symptoms at relapse have a quite favourable outcome after salvage treatment. If their disease is not bulky and is confined entirely to a modest number of previously unirradiated lymph node sites, wide field irradiation offers a reasonable chance of disease control. If their recurrence is bulky, extra-nodal or in a previously irradiated site, the patient's prognosis after HDC/ABMT is excellent. Patients who relapse less than one year after primary chemotherapy or with B symptoms at the time of relapse have a less satisfactory outcome after any available salvage treatment. Trials comparing various HDC/ABMT regimens or novel approaches built on standard dose chemotherapy and irradiation are needed to find better treatments for such patients. Such patients with early or symptomatic relapses who cannot be enrolled in prospective comparative trials should be offered HDC/ABMT while we search for better treatments. Larger trials with a prospective analysis of the risk factors are needed for us to be able to decide which treatment will be the optimal choice for our patients.

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↗
PubMed1993

Is there a role for MACOP-B in the treatment of diffuse large cell lymphoma?

Between 1981 and 1986, 126 patients with advanced stage, large cell lymphoma were treated with MACOP-B chemotherapy. Their six-year failure-free and overall survival is 52% and 62% respectively. Eighty-eight patients aged 60 or less had an excellent six year overall survival of 68%. The outcome for various subsets of patients is analysed according to the number of adverse prognostic factors including age, stage, lactic dehydrogenase level and number of extra nodal sites.

Adult↗
PubMed1993

Allogeneic bone marrow transplantation for poor-prognosis non-Hodgkin's lymphoma.

Twenty-one patients with non-Hodgkin's lymphoma (NHL) felt to be incurable with conventional chemotherapy underwent high-dose chemo +/- radiotherapy and allogeneic sibling donor transplant. The median patient age was 27 years (range 6-47 years); 13 were male and 8 female. By the working formulation, 6 patients at diagnosis had low-grade NHL, 8 intermediate-grade, and 7 high-grade disease. Three patients were in first remission at transplant, 3 in an advanced remission, 5 had failed to respond to initial therapy while 4 had a partial response to initial therapy, and 6 were in relapse (first or beyond). Sixteen patients were conditioned with cyclophosphamide, etoposide and total body irradiation (TBI), 4 with cyclophosphamide and TBI, and one with a combination of busulfan, melphalan and cyclophosphamide. GVHD prophylaxis was variable. At last follow-up, 8 of 21 patients remain alive and progression-free at a median of 37.5 months (range 6-58 months); actuarial event-free survival is 38% (95% confidence interval 17-58%). Thirteen patients died at a median of 2 (range 0.5-8) months post-BMT, 5 from regimen-related toxicity, 3 from acute GVHD, 2 from infections related to chronic GVHD and 3 from disease progression. Factors which were adverse predictors of progression-free survival included low-grade disease, presence of B symptoms at BMT, Karnofsky performance status at BMT and female sex. We concur with previous workers in concluding that allogeneic BMT may offer effective therapy for selected patients with incurable NHL. Major issues to be considered include timing of BMT and disease status at BMT.

Adolescent↗
PubMed1993

Treatment of multiple myeloma with intensive chemotherapy followed by autologous BMT using marrow purged with 4-hydroperoxycyclophosphamide.

In August 1988 we began a program in which multiple myeloma patients achieving < or = 10% marrow plasma cells and > or = 50% reduction in paraprotein levels after the VAD (vincristine, doxorubicin, dexamethasone) regimen underwent bone marrow harvest, ex vivo marrow purging with 4-hydroperoxycyclophosphamide (4-HC) and marrow cryopreservation. Conditioning with a regimen of high-dose busulfan (total dose 16 mg/kg), cyclophosphamide (120 mg/kg) and melphalan (90 mg/m2) (BU + CY + MEL) followed by autologous BMT was then carried out. Seventeen of the 24 patients who received VAD (71%, 95% confidence interval [CI] 49 to 87%) were eligible for bone marrow harvest. One patient was not harvested because of non-medical reasons; two patients who underwent marrow harvest had gross plasmacytosis present in biopsies performed intraoperatively and did not undergo BMT. Fourteen patients (58%, 95% CI 37 to 78%) received BU + CY + MEL and 4-HC-purged autologous BMT. The median time to recovery of 0.5 x 10(9)/l neutrophils was 19 days (range 14 to 26) while the last platelet transfusion was given on a median of day 32 (range 10 to 46) post-BMT in the evaluable patients. The major non-hematologic toxicity was hepatic; two patients in complete remission died of hepatic veno-occlusive disease. Another patient succumbed to fungal infection despite neutrophil recovery. The remaining 11 patients achieved responses (complete in six and partial in five) associated with a normal performance status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Efficacy of weekly cisplatin-based chemotherapy in recurrent and metastatic head and neck cancer.

After disease recurrence or dissemination, patients who had been treated previously with radiation with or without surgery for cancer of the head and neck were given either cisplatin (16 patients), cisplatin/etoposide (15 patients), or cisplatin/etoposide/5-fluorouracil (5-FU) (19 patients) in an ambulatory care clinic. Intravenous (i.v.) cisplatin 25 mg/m2 was given weekly, while etoposide was given i.v. (80 mg/m2) on day 1 and orally (160 mg/m2) on day 2 of every odd-numbered week. In the three-drug regimen, 5-FU 500 mg/m2 i.v. was given every even-numbered week. Patients in all three groups received daily oral prednisone to decrease myelosuppression and oral co-trimoxazole and ketoconazole to prevent infection. The supportive drugs were given to all groups to keep these variables constant. As expected, myelosuppression did not occur in the cisplatin group, while the rates of severe neutropenia (less than 1.0 x 10(9)/L) in the two- and three-drug groups were 26% and 74%, respectively. The incidence of infection requiring hospitalization was low (2.5%). The response rate (complete plus partial) was lowest in the cisplatin group (6%) and higher in the cisplatin/etoposide (47%) and cisplatin/etoposide/5-FU (53%) groups. Because of the low response rate and the short time to progression (5 weeks) in the cisplatin group, 9 of these 16 patients were treated subsequently with cisplatin/etoposide. Time to progression and response duration were similar in the cisplatin/etoposide and cisplatin/etoposide/5-FU groups--12 and 14 weeks, and 12 and 9 weeks, respectively. Median survival times of the cisplatin and cisplatin/etoposide/5-FU groups were 36 and 34 weeks, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Treatment of recurrent and metastatic head and neck cancer with cisplatin/etoposide/bleomycin.

Cisplatin/etoposide/bleomycin (DEB) was given as an outpatient regimen in a novel weekly schedule to 27 patients with recurrent and/or widely metastatic cancer of the head and neck region. Six of these patients also received mitomycin (DEB/M) when their disease failed to respond after at least three weekly DEB doses. All but three patients had been treated previously with radiotherapy directed to the primary site and regional nodal disease; four had also received chemotherapy with cisplatin or carboplatin. Before treatment with DEB, 19 patients had distant metastases. Of an intended 12 doses per patient, a mean of 8.2 was achieved. Myelosuppression was the major toxicity, with neutropenia in 45% of patients and significant anemia in 26%. The overall response rate to DEB in 27 patients was 59%, increasing to 70% after the addition of mitomycin. There were two complete and 17 partial responses. The median duration of response was 12 weeks and median survival was 6 months, with 20% of patients surviving 1 year. We conclude that the relatively short survival time together with the significant toxicity of the DEB/M regimen does not warrant its routine use in clinical practice. However, this regimen, or one patterned on it, should be evaluated in combination with radiotherapy as the initial treatment for selected patients with previously untreated head and neck cancer.

Adult↗
PubMed1991

Outcome of treatment of first relapse of Hodgkin's disease after primary chemotherapy: identification of risk factors from the British Columbia experience 1970 to 1988.

The outcome of treatment for a first relapse of Hodgkin's disease after primary chemotherapy was analyzed in 80 patients. They were divided into four groups: group 1 (n = 24) had initially been treated with three cycles of (mechlorethamine, vincristine, prednisone, and procarbazine [MOPP]) and wide-field irradiation therapy; group 2 (n = 25) had six cycles of MOPP; group 3 (n = 15) and group 4 (n = 16) both initially received MOPP/ABVD (MOPP plus doxorubicin, bleomycin, vinblastine, and dacarbazine) or MOPP/ABV hybrid, but group 3 received conventional salvage regimens whereas group 4 was treated with high-dose chemotherapy and autologous bone marrow transplantation as salvage therapy (n = 16). Freedom from second failure (FF2F) was used as the major endpoint. Actuarial FF2F for all patients was 38% after a median follow-up of 75 months for patients who were alive. Risk factor analysis was performed on the 71 patients who had been treated with curative intent. The presence or absence of any one of three risk factors had a strong negative impact on outcome: stage IV disease at primary diagnosis, B symptoms at relapse, or a time from primary treatment to relapse of less than 1 year. Actuarial FF2F at 5 years was 17% in the group of patients with one or more of these three factors present (n = 49). If none of these factors was present, FF2F was 82% (n = 22) (P less than .001). Even high-dose chemotherapy and autologous bone marrow transplantation were not able to overcome the negative impact of one or more risk factors (FF2F = 19%, n = 12). The outcome of salvage treatments depends most on the presence or absence of these three risk factors and less on the type of salvage treatment. Patients with none of these risk factors present have an excellent outcome if they are treated with non-cross-resistant chemotherapy, or radiotherapy, or both. Novel approaches are needed for patients with one or more of these factors present. Reports on salvage treatments for Hodgkin's disease in first relapse after primary chemotherapy should include data on the proportion of patients having stage IV disease at diagnosis, B symptoms at relapse, and a time from primary treatment to relapse of less than 1 year.

Adolescent↗
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↗