Search PubMed⌕ Search

Biomedical subjects

D Osoba

Publications and source records attributed to D Osoba.

At least 91 records · Page 5Linked to original sources
PubMed1987

Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung.

In order to assess the effect of scheduling of chemotherapy on the outcome of patients with limited small-cell lung cancer (SCLC), the Clinical Trials Group of the National Cancer Institute of Canada carried out a randomized trial comparing the alternation of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH; doxorubicin) and vincristine (CAV) with etoposide (VP-16) and cisplatin for six cycles to the administration of these two combinations in a sequential fashion (three cycles of CAV followed by three of VP-16/cisplatin). Three hundred eligible patients were enrolled on the trial from September 1981 to October 1984. All responding patients were also treated after completion of chemotherapy with thoracic irradiation in randomly allocated doses of 2,000 and 3,750 cGy. The complete response (CR) rate to chemotherapy was slightly, but not significantly, higher on the alternating arm (52% v 44%, P = .20). However, there was no difference in disease-free or overall survival on the alternating and sequential arms, respectively (47.3 weeks v 45.1 weeks, P = .26; 61.7 weeks v 59.5 weeks, P = .56). Data on the effect of radiotherapy dose on survival are not yet mature, but it does not appear the results of this portion of the trial will alter the interpretation of the chemotherapy comparison. Patient characteristics favorably influencing survival were female sex, good performance status, younger age, and absence of supraclavicular node involvement. Two interpretations of these and other results in SCLC are suggested: (1) the difference between the schedules used is too small for the predictions of the Goldie-Coldman model to be realized in a trial of this size, or (2) VP-16/cisplatin is actually a superior regimen and any schedule that exposes patients to these drugs early in treatment will produce improved results.

Adult↗
PubMed1987

Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer. A multicenter, randomized clinical trial by the National Cancer Institute of Canada.

The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%; p less than 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p less than 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.

Adult↗
PubMed1986

Characterization of culture-induced cytotoxicity from human peripheral lymphocyte subpopulations.

Cultured human lymphocyte subpopulations can generate cytotoxicity against K562 leukemia target cells under certain conditions. Such cytotoxicity arises during mixed leukocyte culture or in medium containing fetal calf serum (FCS), mitogenic factors, or interleukin 2. We cultured peripheral blood lymphocytes (PBL) in FCS-containing medium after fractionation of these cells on a Percoll discontinuous density gradient. Higher density cell fractions generated culture-induced spontaneous cytotoxicity (CIC) after 2-3 days in culture. CIC was not due to a loss of suppressor cells during fractionation since culture of PBL prior to fractionation yielded the same results. At least some CIC was associated with the differentiation of higher density cells to newly appearing lower density cells during culture. Most CIC required cells with the HNK-1- OKT3- OKM1+ phenotype. Culture-induced cytotoxicity has some similarities to the previously described lymphokine-activated killing but some important differences are also discussed.

Antibodies, Monoclonal↗
PubMed1986

Canadian cancer care: organizational models.

Canadian cancer care has evolved under systems of provincial and federal fiscal control and aims to optimize the management of patients within each province. In Manitoba, patients are initially assessed at one centre but can subsequently receive chemotherapy at an outreach centre closer to home. In British Columbia, two outreach mechanisms exist: consultative clinics provide consultative and follow-up care by radiotherapists and medical oncologists who travel to outreach centres, and community-based regional oncologists provide diagnostic and treatment services in small communities. In Ontario, peripheral clinics are staffed by oncologists from the two provincial cancer institutions, but efforts have been made to find newer outreach models that will better serve certain communities in that province. Two basic models of cancer care organization in the community presently exist in Canada: one stresses the extension of resources outward to the community from major cancer centres, and the other stresses the support of already established resources in the community. Efforts to coordinate these activities are being initiated.

British Columbia↗
PubMed1986

Combined chemotherapy and radiation therapy for non-small-cell lung cancer.

In a previous study of patients with recurrent or disseminated non-small-cell lung cancer (NSCLC), the combination of bleomycin, etoposide, and cisplatin (BEP) produced objective responses in ten of 17 (59%) patients with large-cell anaplastic carcinoma and in 14 of 35 (40%) with squamous-cell carcinoma. These results prompted a pilot study of combined modality therapy in which two cycles of BEP were administered prior to split-course radiation therapy. Thirty patients with surgically unresectable stage II or III squamous- or large-cell cancer, were entered into the study, of whom 25 were evaluable for response to chemotherapy. One patient (4%) had a complete response (CR), ten (40%) with measureable disease had a partial response (PR), and four (16%) with evaluable disease had significant disease regression prior to radiotherapy (overall response rate, 60%). After radiotherapy, six of 22 (27%) evaluable patients achieved a CR, and six (27%) a PR, for an overall response rate of 55%. Symptom control was achieved with chemotherapy in the majority of patients. The median survival time after the initiation of BEP had not been reached at 52 weeks. The results of this pilot study suggest that a phase III study comparing BEP plus radiation therapy with radiation therapy alone should be undertaken in this subgroup of patients with NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The use of VP-16 plus cisplatin during induction chemotherapy for small-cell lung cancer.

In an attempt to circumvent innate or acquired tumor-cell resistance to chemotherapy, patients with small-cell lung cancer (SCLC) were treated with induction therapy that incorporated two active and potentially non-cross-resistant chemotherapy regimens on two National Cancer Institute of Canada (NCI-C) trials. Patients with limited disease (LD) SCLC were treated with cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) and vincristine (CAV) and VP-16 plus cisplatin in two different sequences. One arm was randomized to receive CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles, and the other arm received three courses of CAV followed by three courses of VP-16 plus cisplatin. Both treatment strategies produced similar response rates and survival curves, and each treatment group has a projected 2-year survival of 20%. Patients with extensive disease (ED) were treated with either six cycles of CAV (standard regimen) or CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles. In this study, the alternating regimen produced a higher complete response (CR) rate (40% v 27%) and overall response rate (61% v 39%; P less than .01). The progression-free survival was also superior for the alternating arm (P = .001), as was overall survival (P less than .05). The frequency of thrombocytopenia and severe gastrointestinal toxicity was slightly greater in the alternating arm, but the frequency of neutropenia and infection was less. The alternation of CAV and VP-16 plus cisplatin during induction therapy is an effective treatment strategy in the management of SCLC and superior to CAV alone in extensive SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

First-line therapy with VP-16 and cisplatin for small-cell lung cancer.

VP-16 and cisplatin were used as first-line therapy in 31 patients with small-cell lung cancer (SCLC) in whom chemotherapy regimens that contained doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) were contraindicated because of severe cardiac or hepatic disease. Eight patients who had cerebral metastases at presentation were also included in the study. There were 11 patients with limited disease (LD) and 20 with extensive disease (ED). Of the 28 evaluable patients, 12 (43%) had a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) failed to respond. The median duration of response (MDR) for LD patients was 39 weeks and for ED patients was 26 weeks. Patients with LD who responded (CR and PR) had a median survival time (MST) of 70 weeks (range, 28 to 232+ weeks), whereas ED patients who responded had an MST of 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. Mild degrees of reversible nephrotoxicity occurred in 15 patients, but required discontinuation of cisplatin in only two. The results of this study are compared with several other recently published reports of VP-16 and cisplatin used as first-line therapy in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Superiority of methylprednisolone sodium succinate over low dose metoclopramide hydrochloride in the prevention of nausea and vomiting produced by cancer chemotherapy.

Methylprednisolone sodium succinate and metoclopramide were compared for their efficacy, tolerance, and safety in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy in patients with cancer. Previously untreated patients about to receive at least 2 cycles of identical chemotherapy were entered into a study using a randomized, double-blind, crossover design. Patients were given either 250 mg of methylprednisolone or 10 mg of metoclopramide intravenously before the first cycle of chemotherapy and were then crossed over to receive the alternate medication before the second cycle of chemotherapy. Prochlorperazine was prescribed in both cycles for postchemotherapy nausea and vomiting. After each treatment cycle patients recorded the degree of nausea, drowsiness and anxiety, the number of episodes of vomiting experienced, and the amount of prochlorperazine taken. After the second treatment cycle patients recorded their preference for either the first or the second antiemetic medication with respect to nausea, vomiting, and overall effectiveness. Of 157 patients entered into the study, 115 were fully appraisable. Methylprednisolone was superior to metoclopramide in preventing nausea and vomiting and in decreasing anxiety and the amount of prochlorperazine used. A majority of the patients expressing a preference preferred methylprednisolone to metoclopramide for control of nausea (p = 0.003), control of vomiting (p = 0.0006), and overall effectiveness (p = 0.00004). There were few side-effects. We conclude that methylprednisolone may have some utility as an antiemetic in patients receiving moderately emetogenic chemotherapy, and who are treated as outpatients.

Antineoplastic Agents↗
PubMed1985

The value of staging and serial follow-up investigations in patients with completely resected, primary, cutaneous malignant melanoma.

The purpose of this study was to determine the value of staging and serial follow-up investigations in newly diagnosed patients with completely excised primary cutaneous malignant melanoma. We reviewed the records of the 393 patients with completely excised primary malignant melanoma who were referred to the Ontario Cancer Institute and the Toronto-Bayview Regional Cancer Centre between 1 January 1978 and 31 March 1982. Initial investigations included history and physical examination in all 393 patients, complete blood count (199 patients), liver function tests (198 patients), urinary melanins (159 patients), chest X-rays (345 patients), whole lung tomography (182 patients), radionuclide liver-spleen scans (207 patients), and bone scans (116 patients), bipedal lymphangiograms (78 patients), CT scans of the chest (59 patients), and CT brain scans (51 patients). The clinical stage of ten patients was changed as a result of history and physical examination or lymphangiogram. All other investigations failed to detect metastatic melanoma. Follow-up investigations included history and physical examinations, complete blood counts, liver function tests, radionuclide liver spleen and bone scans. History and physical examinations, chest X-rays and patients' awareness of abnormalities were responsible for detection of subsequent melanoma recurrences. All other tests failed to identify metastatic melanoma at the time of its occurrence. Therefore, we recommend that initial staging investigations be limited to history and physical examination with clinical photographs, and baseline chest X-ray. We recommend that subsequent follow-up include only history and physical examinations and chest X-rays.

Follow-Up Studies↗
PubMed1985

Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer.

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.

Adult↗
PubMed1985

VP-16 and cisplatin as first-line therapy for small-cell lung cancer.

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.

Adult↗
PubMed1985

Combination chemotherapy with bleomycin, etoposide, and cisplatin in metastatic non-small-cell lung cancer.

Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP). Forty-eight patients were appraisable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for response are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks). Patients with responsive disease survived significantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 16 weeks) (P = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was acceptable. Only four of the 119 treatment cycles were followed by fever even though there was significant neutropenia (0.5 X 10(9)/L) after 20 of 97 treatment cycles. The majority of patients receiving BEP experienced relief of cough, hemoptysis, pain, and fatigue associated with their disease. There was a good correlation between objective responses and palliation of symptoms. Thus, BEP offers good palliation, particularly for patients with squamous-cell and large-cell lung cancer.

Adenocarcinoma↗
PubMed1984

VP-16 alone and in combination with cisplatin in previously treated patients with small cell lung cancer.

Fifty-four patients with small cell cancer of the lung (SCCL) who failed to respond to induction chemotherapy or relapsed within 3 months of its completion were treated either with VP-16 alone or VP-16 and cisplatin. Fifty-two patients were initially treated with cyclophosphamide, doxorubicin (Adriamycin) and vincristine (CAV), and two were treated with cyclophosphamide, methotrexate, and vincristine. Nine patients also received other drug combinations either as maintenance therapy or as treatment for relapse. Fourteen of 18 patients treated with VP-16 alone were evaluable for response, and there was only one partial remission. On the other hand, 15 of the 34 evaluable patients (44%) treated with VP-16 and cisplatin had a partial response, and an additional 11 patients (32%) showed substantial tumor regression and were classified as improved. Two patients had stable disease, and six (18%) progressed. Five of the nine (55.6%) limited-disease patients achieved a partial response compared with 10 of 25 (40%) with extensive disease. The median survival time from the date of first treatment with the combination was 17 weeks (29 weeks for patients achieving a partial response; 19 weeks for those showing improvement; 11 weeks for those with stable disease; and 13 weeks for patients with disease progression). Gastrointestinal toxicity was mild relative to that of CAV-induction therapy but myelosuppression, particularly thrombocytopenia, was common. Mild nephrotoxicity occurred in four patients, but no other important toxicities were identified.

Adult↗
PubMed1982

Failure of short-course multiple drug chemotherapy to benefit patients with recurrent or metastatic head and neck cancer.

Fifty-seven patients with advanced cancer (52 with squamous cell carcinoma of the head and neck) were treated with short-course, multiple drug chemotherapy using schedules that were similar to those proposed by Price et al. Chemotherapy consisted of vincristine, methotrexate and folinic acid rescue, bleomycin, and FU, with or without Adriamycin and hydroxyurea. Most patients had received radiation therapy. There were only six objective responses (one CR, five PR) and except for one patient who is alive without disease following subsequent radiation the remissions were of short duration. Most patients tolerated treatment well but there was one toxic death, two sudden deaths of unknown cause, and renal impairment, mucositis, myelosuppression, or bleomycin skin toxicity in 14 others. Our results differ from those of Price et al. and do not support a role for this type of chemotherapy in the treatment of recurrent or metastatic head and neck cancer.

Antineoplastic Agents↗
PubMed1981

Kaposi's sarcoma complicating corticosteroid therapy for temporal arteritis.

Combination immunosuppressive therapy, particularly in renal transplant recipients, is associated with a higher than expected risk of development of Kaposi's sarcoma, In this report, cutaneous dissemination of Kaposi's sarcoma occurred in a patient with temporal arteritis who was treated with corticosteroids. Reduction of the steroid dosage was followed by regression of the tumor. This sequence of events suggests a causal relationship between the evolution of the sarcoma and corticosteroid therapy. Although Kaposi's sarcoma may complicate corticosteroid therapy alone, the incidence is considerably lower than in renal transplant recipients receiving combination immunosuppressive therapy. Considering the large number of patients with temporal arteritis who are treated with steroids and that this is the first report of its association with Kaposi's sarcoma, it seems that other factors, perhaps genetic, might be important in the development of this neoplasm.

Aged↗
PubMed1980

The prognostic value of HLA phenotypes in Hodgkin's disease.

Analysis of a group of 79 patients with previously untreated Hodgkin's disease, whose HLA phenotypes were determined in 1972-73, shows that patients in a sub-group with the specificities collectively known as Aw19 have significantly poorer survival than patients without these specificities. The degree to which the serologically-detectable HLA antigens assist in determining the prognosis for survival has been analyzed using multiple regression analysis and retrospective stratification. Both approaches indicate that the association of HLA phenotype with survival is not accounted for by correlations between HLA antigens and other know prognostic factors, such as stage, histology, age, and sex. The greatest prognostic value of Aw19 appears to be for patients with relatively unfavorable age (greater than 40 years), stage (III and IV), or histology (lymphocyte depletion, mixed cellularity).

Adult↗