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Mopidamol as adjuvant treatment of non-small cell bronchial carcinoma
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Anronio Curie Hospital of Chest Diseases, Cuneo. Oncology 1989;46: 212-6. Ninety-two nonsmall cell lung cancer (NSCLC) patients were treated wilh a combination chemotherapy containing methotrexate, adriamytin, cyclophosphamide and CCNU (MACC). Theregimen wasadministered in the dose and schedule originally reported. Median survival for all patients was 32 weeks. Only 6 patients demonstrated an objective response with a median survival rate of 5 1 weeks. The remaining 70 evaluable patients were nonrespondcrs. These latter patients had a survivalprobabililyreduced to29wecks. Mcdiantimetoprogressionfor the whole group was 17 weeks. Partial responses were seen in 3 squamous, 1 large cell carcinoma and 1 adenocarcinoma. One patient with bronchiole-alveolar carcinoma had complete disease regression and is still alive 136 weeks after starting treatment. Toxicity was significant with 2 treatment-related deaths. The major toxic effects consisted of myelosupprcssion, nausea, vomiting, and stomatitis. Alopecia was nearly universal; a mild cardiac, renal, or hepatic toxicity was relatively unfrequent. Polychcmotherapy with MACC regimen may benefit a few selected padents with NSCLC, but its overall antitumor efficacy appears to bc very limilcd. Mopidamol as adjuvant treatment of non-small cell bronchial carcinoma Blaha H, Dierkesmann R, Feuerer W et al. Zentrulkrunkenhuus. Gauring. Pneumologie 1989;43:299-304. Between January 1982 and April 1986 a double-blind randomized placeboconuolled study of mopidamol, employed as adjunct therapy to surgery in patients with non-small cell bronchial carcinoma, was performed at 7 hospitals. The main criteria were occurrence of melastases and survival. Mopidamol was given @operatively at a dose of 2 x 150 mg i.v. daily, and postoperatively orally at a dose of 3 x 500 mg daily. The treatment period was scheduled to at least 2 yearsand in some of the patients was prolonged to 3 years. The standard therapy of each individual center was given as basic therapy. A total of 270 patients were included in the study, 147 in the placebo and 123 in the mopidamol group. By the end of the study 52 deaths from metastases had occurred in the placebo group (35%) compared wilh only 32 (26%) in the mopidamol group. This dlffcrcncc is stadstically significant at p c 0.05 withtheone-sidedtest.Acomparisonoflife-tablesaccordingU,KaplanMcier shows a statistically significant dlffcrencc in favour of the group treated with mopidamol (savage p < 0.05). Cox’s multivariate analysis confirmed the statistically sigmficant dlffcrence in favour of the group treated with mopidamol, Ihc inclusion of the risk factors tumour stage and histology in thceva1uaGon results in a p-valueof0.02. With respect to the incldcnce of mclastases thcrc wcrc no appreciable differences between thctreatmcntgroups.TheIncidenccofsideeffectsorundesired events was equal in both groups. The study shows that treatment with mopidamol given as adjunct lhcrapy to surgery leads to a statistically significant prolongation of survival in patients with non-small cell bronchial carcinoma. This prolongation of survival is not associated with any increased risk of adverse reactions.
Chemotherapy plus RA223 in the treatment ofoat cell lung cancer Lipton A, Harvey HA, Walker B et al. Deparrment ofMedicine, The Milton S. Hershey Medical Center, Hershey, PA 17033. Am J Clin Oncol, Cancer Clin Trials 1989;12:259-63. One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vicristine, and etoposide (VP-16)] chemotherapy + RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.
Correlation ofmultidrug resistance with decreased drug accumulation, altered subcellular drug distribution, and increased Pglycoprotein expression in cultured SW-1573 human lung tumor cells Keizer HG, Schuurhuis GJ, Broxterman HI et al. institute of Human Genetics, Free University, 1007 MC Amsterdam. Cancer Res 1989;49:2988-93. Four multidrug-resistant variants of the human squamous lung cancer cell line SW-1573 with levels of doxorubicin resistance ranging from IO- to 2000-fold were characterized with respect to drug accumulation and efflux, subcellular drug distribution pattern, antioxidant defenses, and P-glycoprotein expression. For all these parameters except the antioxidant defenses a correlation was observed with the level of doxorubicin resistance; with increasing drug resistance cellular drug accumulation capacity (as measured for doxorubicin) progressively decreased, initial drug efllux rates (as measured for daunorubicin) progressively increased, while Ihe subcellulardoxorubicm distribution (as mcacured by fluorcsccncc microscopy) gradually shifted from a ‘mainlynuclear’~oa‘main1ycy~oplasmic’pattem.Ourdatasuggestthat in the present set of cell lines the same mechanism of resistance is operating at all levels of doxorubicin resistance. Patients at risk of chemotherapy-associated toxicity in small cell lung cancer Morittu L, Earl HM, Souhami RL et al. Department of Oncology, University College. London W!P RBT. Br J Cancer 1989;59:801-4. During a climcal trial of duration of chemotherapy in small cell lung cancer (SCLC), 7 1 of 610 patients (11.6%)died in the fust 3 weeks. Chemotherapy consisted of cyclophosphamide 1 g m-2 i.v. day 1, etoposide 100 mg I.d.s. orally days l-3, vincristine 2 mg i.v. day 1. The time of dealh was found to be nonrandomly distributed within the first chemotherapy cycle, with a peak incidence between days 7 and 12 after chemotherapy. Patients were matched with controls who the next cases entered into the study who did not die in the first 3 weeks. Patients dying early were more likely to have clinical hepatomcgaly (PC O.OC@l),and ECOG score_ 1 (P~0.00001).Asagroupthesepatientsa1sohadahigher alkalinephosphalase (PC O.OOOZ),an clcvated blood urea(P
Anronio Curie Hospital of Chest Diseases, Cuneo. Oncology 1989;46: 212-6. Ninety-two nonsmall cell lung cancer (NSCLC) patients were treated wilh a combination chemotherapy containing methotrexate, adriamytin, cyclophosphamide and CCNU (MACC). Theregimen wasadministered in the dose and schedule originally reported. Median survival for all patients was 32 weeks. Only 6 patients demonstrated an objective response with a median survival rate of 5 1 weeks. The remaining 70 evaluable patients were nonrespondcrs. These latter patients had a survivalprobabililyreduced to29wecks. Mcdiantimetoprogressionfor the whole group was 17 weeks. Partial responses were seen in 3 squamous, 1 large cell carcinoma and 1 adenocarcinoma. One patient with bronchiole-alveolar carcinoma had complete disease regression and is still alive 136 weeks after starting treatment. Toxicity was significant with 2 treatment-related deaths. The major toxic effects consisted of myelosupprcssion, nausea, vomiting, and stomatitis. Alopecia was nearly universal; a mild cardiac, renal, or hepatic toxicity was relatively unfrequent. Polychcmotherapy with MACC regimen may benefit a few selected padents with NSCLC, but its overall antitumor efficacy appears to bc very limilcd. Mopidamol as adjuvant treatment of non-small cell bronchial carcinoma Blaha H, Dierkesmann R, Feuerer W et al. Zentrulkrunkenhuus. Gauring. Pneumologie 1989;43:299-304. Between January 1982 and April 1986 a double-blind randomized placeboconuolled study of mopidamol, employed as adjunct therapy to surgery in patients with non-small cell bronchial carcinoma, was performed at 7 hospitals. The main criteria were occurrence of melastases and survival. Mopidamol was given @operatively at a dose of 2 x 150 mg i.v. daily, and postoperatively orally at a dose of 3 x 500 mg daily. The treatment period was scheduled to at least 2 yearsand in some of the patients was prolonged to 3 years. The standard therapy of each individual center was given as basic therapy. A total of 270 patients were included in the study, 147 in the placebo and 123 in the mopidamol group. By the end of the study 52 deaths from metastases had occurred in the placebo group (35%) compared wilh only 32 (26%) in the mopidamol group. This dlffcrcncc is stadstically significant at p c 0.05 withtheone-sidedtest.Acomparisonoflife-tablesaccordingU,KaplanMcier shows a statistically significant dlffcrencc in favour of the group treated with mopidamol (savage p < 0.05). Cox’s multivariate analysis confirmed the statistically sigmficant dlffcrence in favour of the group treated with mopidamol, Ihc inclusion of the risk factors tumour stage and histology in thceva1uaGon results in a p-valueof0.02. With respect to the incldcnce of mclastases thcrc wcrc no appreciable differences between thctreatmcntgroups.TheIncidenccofsideeffectsorundesired events was equal in both groups. The study shows that treatment with mopidamol given as adjunct lhcrapy to surgery leads to a statistically significant prolongation of survival in patients with non-small cell bronchial carcinoma. This prolongation of survival is not associated with any increased risk of adverse reactions.
Chemotherapy plus RA223 in the treatment ofoat cell lung cancer Lipton A, Harvey HA, Walker B et al. Deparrment ofMedicine, The Milton S. Hershey Medical Center, Hershey, PA 17033. Am J Clin Oncol, Cancer Clin Trials 1989;12:259-63. One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vicristine, and etoposide (VP-16)] chemotherapy + RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.
Correlation ofmultidrug resistance with decreased drug accumulation, altered subcellular drug distribution, and increased Pglycoprotein expression in cultured SW-1573 human lung tumor cells Keizer HG, Schuurhuis GJ, Broxterman HI et al. institute of Human Genetics, Free University, 1007 MC Amsterdam. Cancer Res 1989;49:2988-93. Four multidrug-resistant variants of the human squamous lung cancer cell line SW-1573 with levels of doxorubicin resistance ranging from IO- to 2000-fold were characterized with respect to drug accumulation and efflux, subcellular drug distribution pattern, antioxidant defenses, and P-glycoprotein expression. For all these parameters except the antioxidant defenses a correlation was observed with the level of doxorubicin resistance; with increasing drug resistance cellular drug accumulation capacity (as measured for doxorubicin) progressively decreased, initial drug efllux rates (as measured for daunorubicin) progressively increased, while Ihe subcellulardoxorubicm distribution (as mcacured by fluorcsccncc microscopy) gradually shifted from a ‘mainlynuclear’~oa‘main1ycy~oplasmic’pattem.Ourdatasuggestthat in the present set of cell lines the same mechanism of resistance is operating at all levels of doxorubicin resistance. Patients at risk of chemotherapy-associated toxicity in small cell lung cancer Morittu L, Earl HM, Souhami RL et al. Department of Oncology, University College. London W!P RBT. Br J Cancer 1989;59:801-4. During a climcal trial of duration of chemotherapy in small cell lung cancer (SCLC), 7 1 of 610 patients (11.6%)died in the fust 3 weeks. Chemotherapy consisted of cyclophosphamide 1 g m-2 i.v. day 1, etoposide 100 mg I.d.s. orally days l-3, vincristine 2 mg i.v. day 1. The time of dealh was found to be nonrandomly distributed within the first chemotherapy cycle, with a peak incidence between days 7 and 12 after chemotherapy. Patients were matched with controls who the next cases entered into the study who did not die in the first 3 weeks. Patients dying early were more likely to have clinical hepatomcgaly (PC O.OC@l),and ECOG score_ 1 (P~0.00001).Asagroupthesepatientsa1sohadahigher alkalinephosphalase (PC O.OOOZ),an clcvated blood urea(P