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Biomedical subjects

M H Cohen

Publications and source records attributed to M H Cohen.

At least 127 records · Page 7Linked to original sources
PubMed1983

Combination chemotherapy of hepatocellular carcinoma with doxorubicin and streptozotocin.

Twenty-three patients with unresectable hepatocellular carcinoma were given doxorubicin 60 mg/m2 I.V. day 1 and streptozotocin 0.5 g/m2 I.V. days 1-5 every 3 weeks. This regimen was chosen because of the activity of doxorubicin and nitrosoureas in hepatocellular carcinoma and the ability to administer both drugs in full doses. Twelve patients were fully ambulatory, 14 had normal serum bilirubin, 11 had pathologic proof of cirrhosis, and 11 had no known extrahepatic tumor dissemination. Partial responses lasting 10 and 14 months occurred in two patients (9%), one had stable disease for 15 months, 12 had documented tumor progression within 4 months, and eight died within 6 weeks of the start of chemotherapy. Median survival of all patients was only 3 months (range 0.3-27), but eight (35%) lived more than 1 year. Of these eight, two responded to doxorubicin and streptozotocin, another two to subsequent chemotherapy, and four had no tumor response whatever. More than 90% of the intended doses of doxorubicin and streptozotocin was administered, with severe leukopenia in three patients, moderate thrombocytopenia in one, and moderate proteinuria in nine. There were no drug-related deaths. Various physical, radiologic, and biochemical parameters were employed in detecting tumor response and progression. Initially abnormal physical examination of the liver, hepatic radionuclide and computed tomographic (CT) scans, and serum alpha-fetoprotein levels improved in both responding patients. Tumor progression was detected by physical examination (7/12), radionuclide (10/12) and CT liver scan (3/7), rising alpha-fetoprotein (5/12), and rising carcinoembryonic antigen (3/8). Physical examination and radionuclide liver scan together documented all tumor response and progression. The combination of doxorubicin and streptozotocin has only modest activity in hepatocellular carcinoma and appears no more active than doxorubicin alone.

Adolescent↗
PubMed1982

The clinical behavior of "mixed" small cell/large cell bronchogenic carcinoma compared to "pure" small cell subtypes.

Biopsy specimens from 19 previously untreated lung cancer patients were prospectively diagnosed as small cell carcinoma with a large cell component. The patients were thoroughly staged and received intensive combination chemotherapy. They represented 12% of all small cell carcinoma cases eligible for aggressive chemotherapy protocols during a 5.5 year period. To determine whether the clinical behavior of this "mixed" histologic variant differed from the other histologic subtypes of small cell lung cancer, we compared these 19 patients to a concurrent group of 103 patients with only small cell cancer in their diagnostic biopsies given equivalent therapy. The "mixed" histology patients were comparable to the "pure" small cell group in age, performance status, extent of disease, and frequency of bone marrow, liver, bone, and central nervous system metastases. Their complete plus partial response rare (58%) was significantly less than the response rate for the "pure" small cell patients (91%), their complete response rate was also lower (16 versus 46%), and their overall survival was significantly shorter (median, 6 versus 10.5 months) Mixed histology small cell/large cell carcinoma represents a distinct pathologic variant of small cell carcinoma of the lung, associated with lower response rates and shorter survival than the "pure" small cell subtypes. Since combination chemotherapy yields some complete responses and long-term disease-free survival in these patients, however, aggressive treatment with potentially curative intent should be considered in their management.

Adult↗
PubMed1982

Abdominal computed tomography in small cell lung cancer: assessment of extent of disease and response to therapy.

Abdominal computed tomography (CT) was performed as part of the initial staging evaluation in 77 patients with small cell carcinoma (SCC) of the lung. CT scans revealed mass lesions in 26 patients (34%). Abnormalities were confined to the liver in 15 patients and to retroperitoneal structures (lymph nodes, adrenal glands, psoas muscle region masses) in eight, and occurred in both areas in three. However, only three of 29 patients otherwise staged as having limited disease (confined to one hemithorax and regional nodes) had evidence of abdominal metastases on CT scan. Most (23/26) positive studies were in patients already known to have more extensive tumor dissemination. In 71 patients with pathologic confirmation of liver status, CT had a sensitivity of 63%, specificity of 91%, and overall accuracy of 85% in assessing the liver. Comparison of radionuclide liver scan findings with hepatic biopsies gave similar results. During therapy, 65 follow-up CT scans were obtained in 46 patients. Scan abnormalities improved or disappeared in 11/12 cases with tumor response documented in other ways, appeared or worsened in 5/13 cases of tumor progression that was diagnosed by other tests, and only rarely (2/65 scans) improved at the time of documented tumor progression, or vice versa. In only three patients, however, did CT scan provide the sole site of evaluable disease during treatment or detect either the only area of residual disease in a patient in otherwise complete remission or the initial evidence of tumor progression. Although abdominal CT scans in SCC can demonstrate metastatic dissemination not evaluable by other means, they provide relatively little therapeutically relevant information beyond that obtained with standard staging procedures.

Abdominal Neoplasms↗
PubMed1982

Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer.

Serum neuron-specific enolase (NSE) levels in 94 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with those in 30 adult controls. 38 of the SCLC patients had limited disease and 56 had extensive disease. Serum NSE was raised (greater than 12.0 ng/ml) in 69% of all patients (mean 52.35 +/- 11.56, range 4.1-850 ng/ml); it was raised in 15/38 (39%) of patients with limited stage disease and in 49/56 (87%) of those with extensive stage disease. Extensive stage patients had significantly higher mean NSE level (59 ng/ml) than did limited stage patients (13.8 ng/ml). Serum NSE was raised in 34/41 (84%) of patients with metastases at 1 or 2 sites and in all patients with metastases at 3 or more sites. Serial measurements in 23 patients receiving combination chemotherapy showed an excellent correlation between serum NSE and clinical response. Continuous cell-lines of SCLC, established from 10 of the patients in this study, all expressed high levels of NSE. These studies indicate that serum NSE may be a useful marker for staging and for monitoring response to therapy in patients with SCLC.

Antineoplastic Agents↗
PubMed1982

Possible enhancement of vincristine neuropathy by VP-16.

Eleven consecutive patients with small cell carcinoma of the lung treated intensively with a combination chemotherapy regimen cyclophosphamide, Adriamycin, VP-16, and vincristine experienced peripheral neuropathy. Four of the 11 patients had severe (Grade III) neuropathy, leaving them virtually bedridden; the remaining seven patients had mild to moderate neuropathy. Only 8 of the 14 patients treated less intensively with vincristine and VP-16 had Grade I and II neuropathy. Predisposing factors for severe neuropathy included advanced age and preexisting peripheral neuropathy. All patients' performance status declined and all lost much weight before developing neuropathy. From accumulated treatment experience of small cell carcinoma with vincristine alone or with vincristine, Adriamycin, cyclophosphamide combinations, the authors feel that the severe neuropathy observed was due to an interaction of vincristine and VP-16. This conclusion is supported by electron microscopic observation of electronopaque granular degeneration of the myelin lamellae of affected nerve fibers.

Aged↗
PubMed1982

Erythroleukemia and other hematologic complications of intensive therapy in long-term survivors of small cell lung cancer.

Eight patients with small cell bronchogenic carcinoma treated with intensive combination chemotherapy, with and without radiotherapy, have been followed for a minimum of two and a half years without relapse. One patient, after a prodrome of macrocytic sideroblastic anemia, leukopenia, and thrombocytopenia, experienced erythroleukemia 34 months after starting chemotherapy, and cytogenetic studies revealed extensive chromosomal abnormalities. Another patient had persistent macrocytic anemia and pancytopenia two years after cessation of therapy. The remaining six patients had normal peripheral blood smears and cell counts. A significant incidence of preleukemia syndromes and acute leukemia appearing as late complications in intensively treated small cell lung cancer patients requires confirmation in larger series of long-term survivors. Prospective determination of marrow karyotype abnormalities may help to identify patients at greatest risk for developing secondary leukemia.

Aged↗
PubMed1982

Discrimination and consistency of five myosin ATPase stains in human normal and Duchenne dystrophic muscle.

Limitations in the ability of the human visual system to assess accurately the relative staining densities of individual fibers in muscle tissue stained for myosin. ATPase can complicate the objective evaluation of fiber type populations. In this study a novel approach is employed which utilizes human visual capabilities to provide accurate fiber classification. Using this approach, the ability of five ATPase staining techniques to discriminate fiber type categories in single samples of human normal and Duchenne dystrophic skeletal muscle is evaluated, as is the consistency of the fiber type classifications between stains. While no major discrepancies in fiber typing were observed in the sample of normal muscle, significant differences in classification, along with a decrease in the ability to discriminate fiber types were noted in the sample of Duchenne muscular dystrophy. For the most part, these discrepancies were resolved by a re-interpretation of the staining characteristics of fibers in one stain.

Adenosine Triphosphatases↗
PubMed1982

ICRF-159 in advanced gastric cancer. Absence of activity.

ICRF-159, and EDTA derivative antitumor agent, was given to 21 patients with advanced gastric cancer in a weekly dose of 3000 mg/m2. Of the 21 patients, 11 had failed prior drug therapies and 10 were previously untreated. No patient achieved an objective partial response (actual response less than 15% with 95% confidence level). One previously treated patient had a minor response lasting 12 weeks and four patients (three previously untreated) had stable disease lasting 4-8 weeks. Toxicity was acceptable, consisting of mild nausea and moderate myelosuppression. Median survival after treatment was 17.5 weeks in previously untreated patients and 9 weeks in previously treated patients. We conclude that ICRF-159 is inactive in advanced gastric cancer when given on a weekly schedule.

Adenocarcinoma↗
PubMed1982

Experience of the National Cancer Institute (USA) in the treatment and biology of small cell lung cancer.

This retrospective study deals with 168 patients with small cell lung cancer (SCLC) who were treated at the NCI March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 per cent of all the patients were disease-free for more than 40 months (25% of the limited disease and 3% of the extended stage disease patients which were treated. Complete remission was essential to prolonged survival. The development of a complete remission was favored by a satisfactory initial general condition, localised disease or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may induce a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This lead the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal cord block above 2 000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are not underway using intensive chemotherapy with multiple tumor site irradiation and autologous marrow implants 48 per cent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease whereas only 40 per cent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. Inspite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI. - Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of APUD system and are secreted by the SCLC. Bombesine has been isolated in all the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. - These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. - In vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). - Lastly, monoclonal AC have been prepared. Inspite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

Antineoplastic Agents↗
PubMed1982

Lack of efficacy of high-dose methotrexate by 30-hour infusion in patients with progressive small cell carcinoma of the lung.

Seventeen patients with small cell carcinoma of the lung (SCCL) refractory to at least one combination chemotherapy regimen were treated with a high-dose methotrexate (HDMTX) program consisting of 1500 mg/m2 of MTX by iv infusion at a constant rate over 30 hrs following a priming dose of 50 mg/m2 of MTX iv. Administration of calcium leucovorin was begun at the end of the infusion. Treatment was repeated every 2 weeks. No complete or partial responses were observed, and the median time to tumor progression was 4 weeks. Hematologic toxicity was much more severe than anticipated, with five patients having thrombocytopenic bleeding requiring platelet transfusions. This HDMTX regimen was both ineffective and unexpectedly toxic in our heavily pretreated patients with SCCL. Literature review discloses little evidence that HDMTX programs have superior activity to standard doses of MTX in this disease.

Carcinoma, Small Cell↗
PubMed1981

Perirectal infections in patients with small cell lung cancer.

Fifteen anorectal infections occurred in 6.4% of 188 intensively treated patients with small cell bronchogenic carcinoma. Granulocytopenia was present at onset in 13 episodes. In eight episodes, perirectal pain preceded any objective findings by two to 11 days. Ten infections resolved with recovery from granulocytopenia, but the five abscesses required incision. Septicemia accompanied four episodes; one patient died. Early recognition and therapy of this potentially fatal infection will become increasingly important as more patients with solid tumors receive intensive therapy.

Abscess↗
PubMed1981

Cure of advanced L1210 leukemia after correction of abnormal red blood cell deformability.

Chemotherapeutic efficacy is inversely related to pretreatment tumor burden. A possible contributory factor in chemotherapy resistance is the occurrence of decreased red blood cell deformability in mice with advanced tumors. Poorly deformable red blood cells may prevent adequate drug delivery to tumor cells. Two methods for improving red cell deformability were found in this study. The first involved treatment of L1210 leukemia-bearing mice with red cell metabolic substrates, including inosine, adenosine, glucose, sodium pyruvate, and ascorbic acid. The combination of inosine plus sodium pyruvate (3 mg of each drug in 0.5 cm3 phosphate-buffered saline) was most effective in restoring deformability to normal. Administration of an active chemotherapeutic agent (BCNU or cyclophosphamide) also improved red cell deformability, with maximal restoration occurring 4--5 days after drug treatment. Standard and 50% of standard drug doses were equally effective in restoring deformability. The optimal therapy program for day 7 L1210 leukemia utilized inosine plus sodium pyruvate given 10--15 min before BCNU 15 mg/kg on day 7 and before BCNU 30 mg/kg on day 12. This treatment yielded 44% cures, whereas BCNU alone, in identical dose and schedule, gave no cures. Median survival was 50 days for the inosine-pyruvate-treated mice, as against 30 days for BCNU alone. Therefore, treatment with non-toxic doses of red blood cell metabolic substrates plus optimal timing of chemotherapy, two maneuvers that significantly increased red blood cell deformability, resulted in significant therapeutic benefit.

Animals↗
PubMed1981

Prognostic implications of stage of disease and sites of metastases in patients with small cell carcinoma of the lung treated with intensive combination chemotherapy.

The influence of various sites of distant metastases on response and survival was analyzed in 106 consecutive previously untreated patients with small cell carcinoma whose disease was systematically staged. All patients received 6 wk of intensive induction chemotherapy with cyclophosphamide, methotrexate, and lomustine; therapy thereafter varied without differential effects on survival. Staging procedures included physical examination, chest roentgenogram, fiberoptic bronchoscopy, bone marrow and liver biopsies, and radionuclide bone, brain, and liver scans. On the basis of pretreatment staging, 33 patients (31%) had limited disease. In the remaining 73 patients, sites of extensive disease included bone in 40; with bone as the sole site of metastatic disease in 13; liver in 30, with liver as the only site in 5; soft tissues in 25 (only site in 7); bone marrow in 22 (only 2); central nervous system in 9 (only site in 4); opposite lung in 7 (only site in 4). Although patients with limited disease live longer than those with extensive disease (median length of survival, 12 versus 10 months), this difference was not significant. This lack of major impact of traditional stage on survival was explained by the similar survival of patients with limited disease and a single site of extensive disease. Prognosis worsened with increasing number of sites of extensive disease (median survival, 11.5, 10, and 8 months for one, two, and three or more sites, respectively). Metastases to the liver or central nervous system significantly shortened survival, whereas involvement of bone, soft tissues, or bone marrow had little adverse effect. In patients with small cell carcinoma whose disease is thoroughly staged and who are given aggressive chemotherapy, certain sites or a small number of sites of extensive disease may be treated as successfully as limited disease.

Aged↗
PubMed1981

Small cell lung cancer: radionuclide bone scans for assessment of tumor extent and response.

Radionuclide bone scans were performed before and during combination chemotherapy in 119 systematically staged patients with small cell carcinoma of the lung. Before therapy, 49 patients (41%) had positive scans. Scan positivity was significantly associated with the presence of metastatic tumor in the bone marrow, positive skeletal radiographs, and elevated serum alkaline phosphatase levels. Nonosseous distant metastases were significantly more likely to be detected as the number of areas of focal abnormalities on bone scan increased. The survival of patients with documented distant metastases in bone and nonosseous sites was significantly inferior to the survival of patients with limited disease, isolated osseous extensive disease, and extensive disease occurring only in nonbony sites. Of 36 patients with initially abnormal scans and tumor regression documented by other methods, scan findings improved in 24 (67%). In 26 (36%) of 72 scans in patients demonstrating disease progression in extraosseous sites, new areas of increased radionuclide uptake appeared. Improvement or worsening in follow-up scans was associated with nonbony tumor response or progression, respectively, 70% of the time. Serial bone scans provide reasonably accurate staging and prognostic information in patients with small cell lung cancer, although they are probably not sufficiently reliable to be used as the sole parameter in therapeutic decision-making.

Antineoplastic Agents↗