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R L Comis

Publications and source records attributed to R L Comis.

At least 91 records · Page 5Linked to original sources
PubMed1986

Oral etoposide in small-cell lung cancer.

Etoposide can be administered orally. On the average, the bioavailability of etoposide administered in a soft gelatin capsule is approximately 50%. For both the oral and intravenous (IV) routes, there is a significant amount of inter- and intrapatient variability. In spite of the variability, clinical studies show that oral etoposide is clearly active in small-cell lung carcinoma (SCLC). In addition, combination chemotherapy studies using etoposide have yielded toxicity equivalent to IV administered programs such as CAV (cyclophosphamide, doxorubicin, vincristine). Oral etoposide has been used in several large combination chemotherapy studies safely and with clear efficacy.

Administration, Oral↗
PubMed1986

Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the colon or pancreas were treated with 400mg of monoclonal antibody 17-1A. This antibody, which binds to a cell surface glycoprotein moiety preferentially expressed by adenocarcinomas of the rectum, colon, pancreas, and stomach, is postulated to induce antibody-dependent monocyte cytotoxicity (ADMC) as a mechanism of tumor lysis. Therapy was preceded by four days of gamma interferon infusions, with the intent of activating peripheral blood monocytes, enhancing monocyte Fc receptor expression and increasing the likelihood of tumor lysis as reflected by enhanced ADMC directed against a colon carcinoma cell line (SW1116) which expresses 17-1A's target antigen. In this Phase I study patients were treated daily at one of the following gamma interferon dose levels (X 10(6) U/M2/day): 0.001, 0.01, 0.1, 1.0, 10.0, 40.0, 60.0, 80.0. Addition of 100 U/ml of rIFN-gamma in vitro to monocytes isolated from normal controls or from patients prior to treatment significantly enhanced monocyte Fc receptor expression and ADMC. in vitro tumor cell killing by monocytes and monoclonal antibody was enhanced by treatment with low doses of rIFN-gamma, while treatment with high doses of rIFN-gamma did not enhance ADMC. No objective clinical responses were noted, although serum tumor markers dropped transiently in 36% of the treated patients. Seven of 11 assayed patients developed human anti-idiotype antibodies. With better scheduling of rIFN- and 17-1A we hope to duplicate optimal in vitro conditions for antibody-mediated cytotoxicity, hopefully enhancing in vivo antibody mediated tumor lysis.

Adenocarcinoma↗
PubMed1985

Impaired interleukin regulation of the phytohemagglutinin response in Hodgkin's disease.

Patients with active Hodgkin's disease (HD) often demonstrate an impaired T-cell proliferative response to phytohemagglutinin (PHA). The present study examined if interleukin regulation of the PHA response was defective in HD. The Hodgkin's PHA response was impaired at all concentrations of PHA utilized. Indomethacin increased the proliferative response but did not bring it to control levels. Stimulation of the cells with both PHA and irradiated Ia+ B cells normalized proliferation despite identical PGE2 concentrations as in the PHA alone cultures. Hodgkin's monocytes produced normal amounts of interleukin 1 (IL-1). Interleukin 2 (IL-2) production by Hodgkin's T cells was decreased in the PHA stimulated cultures, but was normal in the PHA and Ia+ cell stimulated cultures. In response to PHA stimulation alone, Hodgkin's T cells expressed less IL-2 receptor than control cells. The data suggest the diminished PHA response in HD is due to impaired IL-2 production resulting in diminished IL-2 receptor expression. However, when an Ia+ cell source is added to PHA as an additional stimulator, both TCGF production and proliferation are normalized. Monocytes serve to modulate the magnitude of the PHA response through production of both interleukin 1 and PGE2. However, in the presence of sufficient IL-2 production the influence of monocytes is minimized.

Adult↗
PubMed1985

Inverse relationship between constitutive gamma interferon production and human T-cell lymphoma/leukemia virus expression in cultured T lymphocytes.

Particular interest in human T lymphocyte lymphoma/leukemia virus (HTLV) derives from the close association of HTLV with several types of human mature T lymphocyte malignancies and the strong possibility that HTLV is the causative agent of this group of leukemias and lymphomas. This is the first report to show that HTLV expression in T lymphocytes cultured in vitro is inversely proportional to constitutive gamma interferon production. Of 16 fresh T lymphocyte cultures established from patients with mature T lymphocyte neoplasias, 3 were grown continuously for over 3 years and 13 were grown for 2 to 8 months in culture. Of the 16 cultures, 9 were HTLVp19 positive and interferon negative, whereas the remaining 7 were HTLVp19 negative or weakly positive and also interferon positive (12 to 105 U/ml). The prototype HTLV-positive T-cell line (HUT102) was examined over a long-term culture and after selective cell cloning for high virus yield. Results indicate that early-passage, low-HTLV-producing HUT102 cells constitutively produced significant levels of gamma-immune interferon. In late-passage and cloned HUT102 cells, an increase in HTLV production was concordant with a decrease in constitutive interferon production and the loss of mature T lymphocyte antigens. Transformation of human umbilical cord blood lymphocytes by HTLV was possible only after cocultivation with the non-interferon, high virus-producing, cloned HUT102 T lymphocytes. The inverse relationship between interferon and HTLV production was also observed when normal human umbilical cord blood and adult T lymphocytes were transformed by HTLV and maintained in culture.

Adult↗
PubMed1985

Bioavailability and pharmacokinetics of etoposide (VP-16).

The absolute oral bioavailability of etoposide (VePesid) was determined in cancer patients based on a comparison of intravenous and oral administration. The oral dosage unit was etoposide solubilized in a polyethylene glycol-based vehicle in a soft gelatin capsule formulation. The intravenous dose was 80 mg/m2 as a one-hour infusion and the oral dose was 160 mg/m2. The absolute bioavailability based on plasma concentrations or urinary excretion of etoposide was 48% to 57%. The plasma elimination half-life was 5.3 hours, total body clearance 21.4 mL/min/m2, and renal clearance 7.7 mL/min/m2. Significant intersubject and intrasubject variation was observed in intravenous and oral pharmacokinetics and oral bioavailability. This variability could be related to intrapatient and interpatient differences in nonrenal clearance and the inherent patient and disease status problems in evaluating the pharmacokinetics of anticancer drugs. This variability is characteristic of many classes of cytotoxic drugs and indicative of the requirements of individual dose optimization.

Aged↗
PubMed1984

Adverse prognostic effect of N2 disease in treated small cell carcinoma of the lung.

We reviewed survival of patients with clinically localized small cell carcinoma of the lung treated by surgical resection, combination chemotherapy, and prophylactic cranial irradiation. Long-term survival was defined as continuing complete remission 30 months after the start of treatment. Initial TNM staging determined the course of treatment. Ten patients with disease in Stages I and II were treated over 30 months ago by initial resection followed by the full course of chemotherapy. Only one has had a relapse, whereas 80% remained disease-free at 30 months. Five of these patients have passed 5 years. Four patients with T3 N1 disease were treated by two cycles of chemotherapy, surgical resection, and cranial irradiation plus resumption of chemotherapy thereafter; two remained in remission at 30 months. Sixteen patients initially with N2 disease were treated according to the same schedule; 10 of the 16 underwent successful resection. All 16 patients have had a relapse, but the relapse occurred very late in three--at 27, 30, and 37 months. The reasons for the apparently poor prognosis of N2 disease are not clear. Considerations of tumor response kinetics and somatic mutation suggest that these biologic factors are fundamentally responsible. Other studies may find disease control achieved in a very few patients with N2 disease.

Antineoplastic Agents↗
PubMed1984

Histologic alterations in small cell carcinoma of the lung after two cycles of intensive chemotherapy.

In patients treated nonsurgically for "limited" small cell carcinoma of the lung, the most frequent site of relapse is within the chest. We have treated patients with clinical Stage III M0 disease (T3 and/or N2, M0) by two cycles of chemotherapy, surgical resection of the primary site and mediastinal nodes, and continued chemotherapy thereafter. Since May, 1979, the regimen has consisted of cyclophosphamide, doxorubicin, vincristine, and etoposide on a 3 week cycle. The first 12 patients so treated had partial or complete remission after two cycles. Resection was technically not possible in two. Residual small cell carcinoma was not identifiable in the specimens from two of the 10 patients undergoing resection. Microscopic tumor extended to a resection line in two of the eight with residual tumor. Malignant tissue appearing to have the structure of papillary adenocarcinoma was found in hilar and paratracheal nodes in one patient, but nowhere in the resected lung; some residual small cell carcinoma remained in the lung. Nuclear ballooning and eosinophilic inclusions were noted in cells still identifiable as small cell carcinoma in one case. Marked fibrotic scarring was noted in eight cases, acute and organizing bronchopneumonia in three, and multiple small parenchymal abscesses in one case. Long disease-free survival occurred in one patient, in whom residual tumor could not be found in the specimen; in at least one more in whom residual tumor was present; and even in one patient in whom tumor was present at the bronchial resection line.

Aged↗
PubMed1983

The prospect of disease control by surgery combined with chemotherapy in stage I and stage II small cell carcinoma of the lung.

Ten patients with localized small cell carcinoma of the lung (clinical stages I and II) were treated by surgical resection more than 2 years ago; operation was followed by a course of intensive combination chemotherapy. Relapse of the disease has occurred in the central nervous system in 1 patient. One patient died of a surgical complication, and another died more than 4 years later of an unrelated malignancy. All others remain well, and 3 patients have survived longer than 5 years following resection.

Aged↗
PubMed1982

Unusual cause of increased intracranial pressure from metastatic germ cell cancer.

Metastatic lesions within the brain parenchyma are usually responsible for the development of increased intracranial pressure in patients with metastatic cancer. The lesions can usually be easily documented by computerized axial tomography (CT) of the head. Other causes must be sought in patients with metastatic cancer who present with signs of increased intracranial pressure and whose CT scan of the head fails to reveal any parenchymal lesions. Cranial metastases obstructing venous outflow from the brain may present in this manner.

Adult↗
PubMed1982

The development of hyponatremia following combination chemotherapy for metastatic germ cell tumors.

The combination of high dose vinblastine, cisplatin, and bleomycin is an extremely effective, but potentially quite toxic, program for the treatment of metastatic germ cell tumors. In addition to the well-described toxicities, we have noted moderate to severe hyponatremia associated with these drugs. Twelve patients who were receiving this combination chemotherapy program had serum electrolyte levels, plasma osmolality, and creatinine clearance performed prior to and again 5 to 9 days after chemotherapy. Nine of the patients had standard water load tests prior to and again 6 to 15 days after chemotherapy. All 12 patients developed a fall in serum sodium concentrations following chemotherapy, and four patients had severe symptoms attributable to the hyponatremia. Eight patients also developed hypoosmolality suggesting that the hyponatremia was secondary to impaired water handling. In five patients further evidence of impaired water handling was documented by the development of an abnormal standard water load test following chemotherapy. The hyponatremia and impaired water handling may be due primarily to the high doses of vinblastine in the chemotherapeutic program. Patients who are receiving this combination chemotherapy program should be observed for the development of hyponatremia. The presence of severe, symptomatic hyponatremia and impaired water handling may require appropriate treatment including water restriction and hypertonic saline administration.

Adult↗
PubMed1982

Detection of a serum DNA-binding protein associated with cancer.

An accompanying report describes the purification and partial characterization of a unique DNA-binding protein (Mr 64,000; pI 5.9) that is present in human sera. This report gives the results of assays of sera from patients for the bleomycin inhibitor protein (BIP) using the Pseudomonas bacteriophage covalently closed circular DNA fluorescence technique standardized for DNA breakage induced by bleomycin. The results of the BIP assays were expressed by values of specific activity of inhibition. One arbitrary unit of inhibitory activity was defined as equivalent to the amount of serum protein required to cause 50% inhibition of DNA degradation using standard conditions of the DNA breakage assay. The mean values of specific activity of inhibition (SAI) for groups of healthy individuals (n = 26), patients with nonmalignant diseases (n = 33), and patients with malignant diseases (n = 83) were 12.60 +/- 4.69 (S.E.), 12.53 +/- 3.17, and 2.40 +/- 0.84 units/mg, respectively. Mean SAI values for patients with cancers of various types were: solid tumors (n = 46), 2.44 +/- 0.86; leukemias (n = 24), 2.59 +/- 0.96; and lymphomas (n = 18), 2.07 +/- 0.64. The decrease in BIP activity was not correlated with sex, age, or prior chemotherapy. Mean SAI values of male (n = 29) and female (n = 59) patients with cancer were 2.61 +/- 0.87 and 2.30 +/- 0.83 units/mg, respectively. Mean SAI values for different age groups were: 0 to 40 years (n = 21), 2.05 +/- 0.68 units/mg; 41 to 70 years (n = 56), 2.59 +/- 0.68 units/mg; and greater than 70 years (n = 11), 2.12 +/- 0.67 units/mg. Cancer patients with and without prior chemotherapy had mean SAI values of 2.97 +/- 0.85 (n = 23) and 2.20 +/- 0.86 units/mg (n = 65), respectively. Linear regression analysis comparing SAI values and serum protein levels showed no correlation (r = 0.21). These results suggest the decrease of the BIP is associated with malignant disease. Additional controlled studies are required before the significance of this association can be adequately assessed.

Adolescent↗
PubMed1982

Phase II trial of extended indications for resection is small cell carcinoma of the lung.

Surgical resection offers distinct theoretical advantages as the "local" modality in treatment of Stage I and II small cell carcinoma of the lung. We have treated 10 such patients by initial resection since 1975; all survivors but one received adjuvant chemotherapy for the full course thereafter. One patient died of a pulmonary embolus; the other nine remain without evidence of disease from 7 to 69 months after resection. A trial was undertaken of extended indications for resection in selected patients with Stage III-M0 disease. Criteria for patient selection have been developed gradually; these exclude patients for reasons of refusal, physiological inadequacy, disease unsuited to gross total eradication, or lack of adequate initial response to chemotherapy. Of six patients who survived the exclusion criteria and underwent resection, one has had a relapse at 26 months. All others remain without evidence of disease, 5 to 25 months after the start of treatment. We believe that systematic patient selection on the basis of defined criteria will identify a subset of patients having markedly improved chances for disease control. This group may represent as many as half of the patients first presenting with localized or MO disease. Patients excluded as candidates for resection have continued to receive standard nonsurgical combined-modality therapy.

Carcinoma, Small Cell↗
PubMed1982

Small cell anaplastic carcinoma of the lung. The Cancer and Leukemia Group B Experience.

Three protocols have been evaluated by the Cancer and Leukemia Group B (CALGB) for the treatment of small cell anaplastic cancer of the lung between 1972 to 1980. The first protocol (CALBG 7283) was a randomized comparison between 4 arms: high dose cyclophosphamide alone, cyclophosphamide plus methotrexate, cyclophosphamide plus methotrexate plus vincristine, and cyclophosphamide plus high-dose methotrexate plus vincristine. Response rate and survival were not significantly different among the 4 arms. Effectiveness of prophylactic brain radiotherapy and usefulness of maintenance chemotherapy were demonstrated. The next protocols (CALGB 7781 and 7782) compared two adriamycin containing regimens: MACC (methotrexate, adriamycin, cyclophosphamide, CCNU) versus CCV/AV (cyclophosphamide, CCNU, vincristine, alternating with adriamycin and vincristine). Split course radiotherapy (total 45 Gy over 4 weeks) was also given to all patients with limited disease (CALGB 7781) as well as prophylactic brian irradiation. Radiotherapy to the chest was also given in an additional arm of CALGB 7782 for patients with extensive disease. No significant differences were seen for response and survival within categories defined by extent of disease. Overall about 25 per cent of patients achieving complete remission remain alive at 2 years. The prognostic impact of different factors including extent of disease, performance of status, age and sex are discussed.

Antineoplastic Agents↗
PubMed1982

Severe neurotoxicity with methyl G: CALGB experience.

Methylglyoxal bis-dihydrochloride is a drug that has been available for use in cancer chemotherapy since 1955. In earlier studies, it was used on a daily schedule with resulting severe gastrointestinal toxicity and myelosuppression. To avoid that toxicity, a new weekly schedule has been adopted in several Phase II studies. With the weekly schedule, new types of toxicity have been described and we report four patients who have developed a severe sensory-motor neuropathy with the chemotherapy which appears to be drug-related.

Aged↗