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Biomedical subjects

M J Matthews

Publications and source records attributed to M J Matthews.

At least 37 records · Page 2Linked to original sources
PubMed1983

High-dose methotrexate with leucovorin rescue in patients with unresectable non-small cell carcinoma of the lung.

Thirty-one patients with unresectable non-small cell carcinoma of the lung (19 adenocarcinoma, 7 large cell carcinoma, 4 squamous cell carcinoma, 1 mixed histology) were treated with one of two intravenous infusion schedules of high dose methotrexate with leucovorin rescue. First, 14 patients received methotrexate in escalating doses from 1.5 to 12 g/m2 over 6 hours followed immediately with leucovorin 15 mg/m2 for 12 doses every 6 hours; there were no complete or partial responses among these 14 patients. Then, 17 patients were treated with a loading bolus of 50 mg/m2 intravenous methotrexate followed by a 30-hour continuous infusion of 1.5 g/m2. Leucovorin 15 mg/m2 every 6 hours for 12 doses was begun at the end of the infusion. There were 3 partial responses among the 17 patients in this group. The results demonstrate that both 6- and 30-hour infusions of high-dose methotrexate regimens can be given safely to middle aged adult patients, but the overall 10% response rate does not appear to be significantly different than the results with standard-dose methotrexate.

Adenocarcinoma↗
PubMed1983

Delayed hypersensitivity skin testing as a prognostic indicator in patients with small cell lung cancer.

The prognostic importance of pretreatment delayed hypersensitivity skin test reactivity was determined in 154 newly diagnosed, carefully staged and aggressively treated small cell lung cancer patients. One hundred twenty-one patients were reactive to at least 1 of 5 skin test antigens and 33 were anergic. Skin test reactive patients survived significantly longer than anergic patients. This result was expected since there was a significant trend for reactive patients to have good performance status (P = 0.005) and low tumor burden (P = 0.005) compared to anergic patients. The principal finding of this study was that skin test reactivity was of prognostic utility primarily in otherwise good prognosis patients, i.e., individuals with good performance status and low tumor burden. In this group anergy was associated with significantly shortened survival (P = 0.025). In poor prognosis (poor performance status and high tumor burden) or intermediate prognosis (either poor performance status or high tumor burden) patients skin test reactivity or anergy had no significant influence on survival.

Adult↗
PubMed1983

Clinical course of retrovirus-associated adult T-cell lymphoma in the United States.

We studied the clinical features of 11 patients with adult T-cell lymphoma associated with the human T-cell lymphoma virus. The patients were predominantly young, black, and born in the southeastern United States. They had an aggressive course, with the rapid onset of disseminated skin lesions or symptoms related to hypercalcemia and other metabolic disturbances, or both. Common findings included rapid enlargement of peripheral, hilar, and retroperitoneal lymph nodes, with sparing of the mediastinum; invasion of the central nervous system, lungs, or gastrointestinal tract; and opportunistic infections. A paraneoplastic syndrome characterized by increased bone turnover, abnormal bone scintigraphy, and hypercalcemia was present in all patients. Intensive combination chemotherapy produced prompt complete clinical remissions, which were generally of short duration. Similar features have been described in patients in Japan and the West Indies who had adult T-cell lymphoma, which is also associated with the human T-cell lymphoma virus. This syndrome should be suspected in patients presenting with the acute onset of widespread T-cell lymphoma in association with metabolic bone disease and hypercalcemia. The presence of the syndrome can be confirmed by appropriate serologic and virologic studies.

Adult↗
PubMed1983

Treatment of extensive stage small cell bronchogenic carcinoma. Effects of variation in intensity of induction chemotherapy.

Forty-nine consecutive previously untreated patients with extensive stage small cell bronchogenic carcinoma were treated with cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, etoposide (VP-16-213) 125 mg/m2, and vincristine 1.4 mg/m2 (maximum 2 mg) as induction chemotherapy. Thirty-four patients were given high-intensity therapy, receiving these drugs on both Days 1 and 8 of two or three 21-day induction courses. Fifteen other patients were treated with moderate intensity, receiving these drugs only on Day 1 of two 21-day induction courses. The number and intensity of induction courses were determined by the time of entry into the study. There were 31 complete or partial remissions among the 33 evaluable patients treated with high-intensity therapy (94 percent), including eight complete remissions (24 percent), whereas there were 11 responses (73 percent) including three complete responses (20 percent) among the 15 patients treated with moderate-intensity therapy. There was no marked tendency for the patients in the high-intensity group to have a more favorable response to the induction chemotherapy (p = 0.22), and survival experience was very similar in the two groups (p = 0.92). Overall median survival was 12 months. Within the high-intensity group, there was no significant difference between patients receiving two or three courses of induction therapy with respect to response (p = 0.97) or survival (p = 0.32). There were six induction deaths in the high-intensity induction group (18 percent) and one induction death in the moderate-intensity group (7 percent) (p = 0.59). In addition to the expected hematologic and infectious complications, there were unexpectedly high frequencies of mucositis, reversible congestive heart failure, and severe peripheral neuropathy in patients treated with high-intensity induction. Only two patients, both in the high-intensity group, were alive and free of disease at 24 months. Increasing the intensity of induction chemotherapy with these drugs did not significantly improve response or survival in extensive stage small cell bronchogenic carcinoma.

Adult↗
PubMed1983

Chemotherapy-induced pulmonary toxicity in mice bearing L1210 leukemia.

Fatal pulmonary toxicity can be consistently produced in L1210 leukemia-bearing mice by single therapeutic doses of cyclophosphamide, BCNU, and mitomycin C but not by adriamycin. Lung toxicity is principally determined by an existing tumor burden at the time of drug administration. Thus when any of the four chemotherapeutic agents was given 5 days after L1210 transplantation there was no mortality. Pulmonary pathology in these mice was equivalent to that noted in normal mice receiving identical drug treatment or to that noted in untreated L1210-bearing mice sacrificed 7, 8, or 10 days after tumor transplantation. When chemotherapy was delayed to day 7 after L1210 transplantation for mitomycin C or to day 8 after transplantation for BCNU and cyclophosphamide, more severe pulmonary toxicity was found. Mortality within the first 5 days of treatment was 38, 50, and 80%, respectively. Pulmonary pathology included moderate to severe vascular congestion and interstitial pneumonitis, diffuse pulmonary hemorrhage often involving the entire pulmonary parenchyma, pulmonary edema, and alveolar cell metaplasia. A unique finding, associated with cyclophosphamide treatment, was the occurrence of perivascular-intramural edema of the walls of medium-size pulmonary vessels. It is hypothesized that stasis within the pulmonary capillary circulation, resulting from advanced tumor growth and from drug treatment, may contribute to the development of chemotherapy-related toxicity.

Animals↗
PubMed1983

Diagnostic and biological implications of flow cytometric DNA content analysis in lung cancer.

Flow cytometric DNA content analysis, performed on clinical specimens from patients with lung cancer, was compared with clinical features, histological and/or cytological examination of the same specimen and, in some instances, to chromosome analysis and repeat DNA content analysis of short-term cultures. Tumors from 85% of non-small cell and 83% of small cell lung cancer patients had aneuploid DNA content; multiple aneuploid stem lines were present in 11% of patients. Comparisons with microscopic examination showed that aneuploid cells were detected in 122 of 167 clinical samples containing tumor cells and in 3 of 177 samples microscopically free of tumor. The high false-negative rate, shown to be due in large part to the presence of near-diploid tumor cells, makes single-parameter DNA analysis impractical for use in automated cytology. Short-term cultures of tumor cells, used to confirm that tumors had DNA content indistinguishable from diploid, demonstrated a single near-diploid peak on repeat DNA analysis with or without the addition of diploid lymphocytes and internal DNA standards. Chromosome banding studies showed clonal structural abnormalities with minimal numeric alterations. Survival of small cell lung cancer patients was similar for patients with near-diploid and aneuploid tumors. Cell cycle analysis could be performed in only a minority of samples, and there were no apparent differences in the proliferative fraction between lung cancer cell types. We conclude that flow cytometric DNA content analysis provides useful biological information and is a useful marker for following tumor cell cultures, but multiparameter analyses will be required for use in automated cytology and in cell kinetic studies.

DNA↗
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

Prolonged intermittent adjuvant chemotherapy with CCNU and hydroxyurea after resection of carcinoma of the lung.

Eight hundred sixty-five patients with a microscopically curative resection for carcinoma of the lung were accepted for study, none of whom were excluded from analysis. Adjuvant therapy was randomly assigned about the tenth to 14th postoperative day; 432 patients (treated) were to receive CCNU and hydroxyurea for one year, while 433 patients (controls) were to receive no adjuvant therapy. Toxic reactions to therapy were reported, but only 1% were severe enough to require stopping therapy. No evidence of improved survival or delayed recurrence of disease was seen in treated patients as a whole or when examined by cell type and by postsurgical TNM category. On the contrary, survival beyond the second year of follow-up may have been impaired by the drugs when administered to patients without evidence of tumor spread to the lymph nodes.

Carcinoma↗
PubMed1982

Clinical implications of cytogenetic studies in cutaneous T-cell lymphoma (CTCL).

Detailed cytogenetic studies were performed in 41 patients with cutaneous T-cell lymphoma (CTCL): four patients had limited plaques, 13 patients had generalized plaques, eight patients had cutaneous tumors, 16 patients had generalized erythroderma, and four additional patients, who had relatively benign chronic dermatosis, served as controls. Correlating the histologic and cytogenetic results in the various tissues, it was observed that 62% of the peripheral blood specimens were cytogenetically positive but only 49% were morphologically positive; in the lymph node the ratio was 80 versus 45%, and in the bone marrow, 6 versus 3%. These studies demonstrate that chromosome abnormalities are frequently detectable before morphologic changes become apparent. Chromosome banding preparations showed extensive and wide-ranging heteroploidy; the #1 chromosome was most frequently involved in structural abnormalities while chromosomes #11, 21, and 22 were most frequently involved in numerical abnormalities. These cytogenetic findings support the impression that CTCL is a disease whose various clinical manifestations represent a chronologic sequence, with the cytogenetic findings paralleling the clinical symptoms: patients with minimal chromosomal changes had the best survival and the more extensive the chromosome abnormalities, the more advanced the clinical disease. Clone formation was seen in eight patients and this phenomenon, along with hyperdiploidy and near-tetraploidy, was associated with a poor prognosis and short survival. We conclude that CTCL progresses from an early phase with extensive chromosomal abnormalities and lack of clone formation to a terminal phase with clone selection. Cytogenetic studies can, therefore, be of significant diagnostic and prognostic value in CTCL.

Adult↗
PubMed1982

Histopathologic classification of small cell carcinoma of the lung: comments based on an interobserver examination.

In order to evaluate the consistency in diagnosing the morphologic subtypes of small cell carcinoma of the lung (SCCL), 93 microscopic slides were blindly classified by three panelists according to the World Health Organization's (WHO) Lung Tumor Classifications of 1967 and 1981. Unanimity in the diagnosis of SCCL as the main cell type was obtained in 91 and 94% respectively. With regard to the diagnosis of the various morphologic subtypes unanimity among the three panelists was achieved in 38% according to the WHO 1967 classification and in 54% using the 1981 classification. It is concluded that the criteria used for SCCL as a distinct histopathologic entity were reproducible among the different panelists. However, different criteria were applied in the diagnosis of the morphologic subtypes of SCCL. This fact could explain the contradictory results of clinical studies reported in the literature concerning subtyping of SCCL.

Autopsy↗
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

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

Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience.

CLM developed in 60 of 526 patients (11%) with SCLC seen at the NCI between August 1969 and June 1980. Life table analysis revealed an overall 25% risk of CLM at 3 years. CLM was diagnosed during all phases of the patients' clinical course, but the majority (83%) were cases diagnosed at the time of progressive systemic disease. Univariate log rank analysis indicated that pretreatment factors associated with the development of CLM included: involvement of the brain, spinal cord, bone marrow, liver or bone; extensive disease; and male sex. Patients who did not obtain a complete response to systemic therapy were at greater risk of developing CLM than complete responders. Multivariate analysis of these factors indicated that liver metastases were most strongly associated with the time to development of CLM, followed in order of importance by bone and CNS metastases. Patients usually presented with signs and symptoms reflecting involvement of multiple areas of the neuraxis including the cerebrum, cranial nerves and spinal cord; 51 of the 60 patients had intracerebral metastases and 27 had spinal cord lesions during their clinical course. Autopsy features including focal or diffuse involvement of the leptomeninges with infiltration of the Virchow-Robin spaces were similar to meningeal lymphoma and leukemia, except that CLM was rarely the sole manifestation of CNS tumor. Median survival following the diagnosis of CLM was 7 weeks. However, most deaths were attributed to systemic disease, and treatment with intrathecal chemotherapy and irradiation often provided palliation. With the increased awareness of this complication, an antemortem diagnosis increased from 39% prior to 1977, to 88% of patients after 1977.

Adult↗
PubMed1982

Sleep-associated gonadotrophin and oestradiol patterns in girls with precocious sexual development.

Circulating concentrations of gonadotrophins and oestradiol (E2) during sleep were examined in six girls aged 5-10 years with precocious sexual development. All subjects exhibited nocturnal increments of LH and/or FSH. Gonadotrophin secretion appeared to vary from pulsatile release to random oscillations. Three subjects with LH pulses of greater than 5 miu/ml and a concomitant FSH rise had a temporal elevation of E2 during sleep. The other three subjects with pulses of either LH or FSH of less than 5 miu/ml had no nocturnal rise in E2. These data suggest that the nocturnal elevation of E2 results from pituitary release of both LH and FSH, leads to premature sexual development, and may be occasioned by inappropriate timing of hypothalamic gonadotrophin-releasing hormone (LHRH) secretion.

Child↗