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Biomedical subjects

J M Connors

Publications and source records attributed to J M Connors.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1991

A current analysis of primary lymphoma of the thyroid.

Over a 9-year period ending in May 1990, 27 patients with histologically proved thyroid lymphoma were assessed and treated. There were 24 female and three male patients with a median age of 67 years at the time of diagnosis (age range, 39 to 85 years). The usual presentation was that of a rapidly enlarging neck mass. Incisional biopsy was the diagnostic procedure of choice; however, nine of 27 patients underwent diagnostic partial or total thyroidectomy based on a preoperative impression of thyroid carcinoma. All 27 patients had non-Hodgkin's lymphomas of intermediate (77%) or high (23%) grade. Detailed staging was carried out in 25 patients; seven patients (28%) had disease confined to the thyroid gland (stage I), while 18 (73%) had accompanying disease in cervical lymph nodes or the mediastinum (stage II). Combined multiagent chemotherapy and irradiation was given to 19 of 25 staged patients (76%). Actuarial, overall 5-year survival for all patients was 70% with 48 months being the median follow-up for living patients (follow-up range, 3 to 102 months). Of a number of factors evaluated using log-rank survival tests, only the absence of dysphagia at the time of hospital admission, a primary tumor mass not greater than 10 cm, restriction of disease to the thyroid gland, and the absence of mediastinal lymph node involvement were statistically significant predictors of improved survival. Surgery should usually be restricted to diagnostic biopsy, as there is infrequently a role for resection in the management of thyroid lymphoma, given the effectiveness of combined multiagent chemotherapy and radiotherapy.

Actuarial Analysis↗
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

Compensatory changes in thyroid blood flow are only partially mediated by thyrotropin.

It has been shown that the compensatory growth of the thyroid gland and the compensatory increase in hormone secretion that occur after hemithyroidectomy are preceded by a dramatic increase in thyroid blood flow (BF). These alterations in the thyroid remnant may be due to the concomitant increase in plasma thyrotropin (TSH) concentrations. It has been suggested, however, that the compensatory thyroid growth may also involve a neural reflex. In this study we have investigated the role of TSH in mediating the compensatory alterations in thyroid BF and mass after subtotal thyroidectomy. Male Sprague-Dawley rats were anesthetized with ether for surgical or sham hemithyroidectomy. One-half of the hemithyroidectomized rats (HTX) received no further treatment; in the other one-half of the HTX rats (Clamp), plasma TSH levels were maintained at levels comparable with those in sham-operated animals by initiating constant thyroid hormone replacement beginning at the time of hemithyroidectomy. Plasma samples for TSH, 3,5,3'-triiodothyronine, and thyroxine radioimmunoassays were obtained 2, 7, 14, and 21 days after surgery. Thyroid BF was determined at 1, 2, and 3 wk after surgery by the reference sample version of the radioactive microsphere technique (141Ce, 15 microns diameter). Plasma TSH levels and thyroid lobe weight were significantly elevated in HTX rats but not in Clamp rats. Thyroid BF was markedly increased in HTX rats. Thyroid BF was also significantly increased in Clamp rats despite the suppression of the rise in plasma TSH concentration, but this increase was less than that in HTX rats. Neither hemithyroidectomy nor Clamp treatments had any effect on arterial blood pressure or BF to other tissues (e.g., kidney).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Muscarinic modulation of the vasodilatory effects of vasoactive intestinal peptide at the rat thyroid gland.

In the thyroid gland, vasoactive intestinal peptide (VIP) and acetylcholine (ACh) are found in nerve fibers associated with secretory cells and blood vessels. We have, therefore, initiated studies to explore the actions of and interactions between cholinergic agents and VIP in the regulation of thyroid vascular conductance (VC). Thyroid and other organ blood flows were measured using radiolabelled (141Ce) microspheres injected directly into the left cardiac ventricle of anesthetized male rats. The mean systemic arterial pressure was monitored and used in the calculation of organ VC (blood flow/arterial pressure). Plasma TSH, T3, and T4 levels before and after infusions were measured by RIA. The acute administration of ACh (3 x 10(-8) mol/100 g BW) over 4 min increased thyroid VC, whereas nicotine (10(-7) mol/100 g BW) had no such effect. Circulating TSH and thyroid-hormone levels following ACh or nicotine were not different from those in vehicle-treated animals at 20 min or 2 h after infusion. This observation suggested that ACh acts through muscarinic receptors at the thyroid gland to increase VC. In order to extend these observations and to evaluate whether VIP might exert any of its thyroidal effects on VC via muscarinic receptors, we assessed the effects of ACh, methacholine chloride (MCC), and VIP in the presence and absence of the muscarinic receptor blocker atropine. Rats were treated intravenously with saline or atropine (3 mg/kg) 20 min before intravenous infusions of vehicle, ACh (3 x 10(-8) mol/100 g BW), MCC (5 x 10(-9) mol/100 g BW), or VIP (10(-11) mol/100 g BW).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease.

Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy.

Adolescent↗