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Biomedical subjects

L Nathanson

Publications and source records attributed to L Nathanson.

At least 73 records · Page 4Linked to original sources
PubMed1980

Pilot study of vinblastine and bleomycin combinations in the treatment of metastatic melanoma.

Fourteen patients with advanced metastatic malignant melanoma were entered in a study with a combination of vinblastine and bleomycin (11 patients) or with this combination plus cis-dichlorodiammineplatinum(II) (three patients). Objective partial responses were seen in four of nine evaluable patients receiving vinblastine and bleomycin and in all three evaluable patients receiving vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II). Although there was significant toxicity, it appeared tolerable, and no drug deaths were reported. The three drug-combination may produce less severe toxicity while maintaining a high response rate.

Bleomycin↗
PubMed1980

Trifluoperazine reversal of secretory diarrhea in pancreatic cholera.

Diarrhea in a patient with pancreatic cholera syndrome caused by a vasoactive intestinal polypeptide producing pancreatic islet-cell carcinoma responded rapidly and dramatically to the phenothiazine trifluoperazine. Treatment with intravenous somatostatin decreased the plasma vasoactive intestinal polypeptide level without changing the diarrhea. The chemotherapeutic agent chlorozotocin, the 2-chloroethyl analogue of streptozocin, caused a decrease in plasma vasoactive intestinal polypeptide but caused significant renal toxicity with proteinuria.

Adenoma, Islet Cell↗
PubMed1979

High dose methotrexate with and without BCG therapy in advanced head and neck malignancy.

Twenty-three patients with advanced recurrent head and neck carcinoma were randomized to receive either high dose methotrexate with calcium leucovorin rescue (HDMTX) or HDMTX in combination with bacilli Calmette Guerin (HDMTX/BCG). An additional eight patients were treated with escalating doses of HDMTX ranging from 1 to 7 g of methotrexate. Of 12 patients receiving HDMTX, one complete response and two partial responses were noted. Of 11 patients in the HDMTX/BCG group, one complete response and two partial responses were observed. Only one partial response was noted in eight patients receiving escalating doses of the drug. Responses were brief and no significant difference in response duration was seen in any particular group. Toxicities in all groups were tolerable. BCG did not improve response rate, median duration of response, or median survival in these patients. Reported experiences with high dose methotrexate have been reviewed and again, responses to "high dose methotrexate" were found to be of brief duration. Despite acceptable toxicity, the brief duration of response and cost of such therapy raises serious question on the usefulness of chemoimmunotherapy utilizing high dose methotrexate with leucovorin rescue and BCG in the management of advanced recurrent carcinomas of the head and neck region.

Adult↗
PubMed1979

Prospective comparison of intralesional and multipuncture BCG in recurrent intradermal melanoma.

Fifty-nine patients with metastatic melanoma predominantly localized in the skin were randomly assigned to treatment with BCG given either intralesionally (IL-BCG) or by multiple puncture vaccination at a nontumor bearing site in the skin (MPV-BCG). Half the patients with IL-BCG experienced moderate fever, chills and malaise, suggesting systemic exposure to this live organism. However, only three of these patients required systemic antituberculous chemotherapy and all responded to it. MPV-BCG treated patients experienced significantly less systemic toxicity. Among fully evaluable patients 45% objective response rate was seen in the IL-BCG group and a 9% response rate in the MPV-BCG group, a significant difference. The only complete responses were seen in the IL-BCG group. Among fully evaluable patients, median survival was 21.1 months in the IL-BCG group and 13.3 months in the MPV-BCG groups (NSD). No patients with pretreatment anergy to all skin tests utilized, experienced objective response to BCG.

Adult↗
PubMed1979

Immunotherapy of melanoma.

Malignant melanoma is a disease characterized by clinical evidence of host defense, possibly immunologically mediated. It is a disease which tends to be refractory to both radiotherapy and chemotherapy. Immunotherapy has been used in three phases of the disease. 1. Intralesional immunotherapy with a nonspecific immune adjuvant in patients with local intradermal or soft tissue recurrence. This treatment produces approximately 15% regression of both injected and uninjected lesions, and about 60% regression of injected lesions only. Both clinical and laboratory evidence suggests that this regression is immunologically mediated. 2. Patients with surgical removal of all clinically demonstrable tumor, either primary disease alone or regional node recurrence, active nonspecific, and specific, immunotherapy has been used in an adjuvant setting. There is considerable controversy about the benefits accruing to such immunotherapy, but most large scale prospective and randomized studies have suggested that if benefit does result it is modest in degree and probably cannot be measured in terms of increase in cure rate. 3. Immunotherapy has also been used as a nonspecific active adjuvant to single drug or polychemotherapy in patients with disseminated melanoma. Whereas complete response rate may be slightly increased by this maneuver there is no convincing evidence that immunotherapy markedly increases the total objective response rate to polychemotherapy, and survival is only marginally superior when immunotherapy is added to chemotherapy in this setting. Further studies need to be done with active specific immunotherapy with tumor cell membrane extracts; as an adjuvant in patients with minimal body burden of tumor cells; and to study the inaction between chemotherapy and immunotherapy in this disease. Furthermore, studies of chemically defined fractions of either bacterial cell wall or tumor cell extracts must be evaluated both in terms of their ability to augment cell mediated immune responses in the melanoma patient, and also in terms of their ability to induce objective benefit for the patient. The possible use of immunotherapy in patients with primary melanoma has been briefly explored but needs further study. Possible additive effects with radiotherapy and immunotherapy should also be looked at in this disease utilizing high dose fractions and other new forms of radiotherapeutic technique.

Adjuvants, Immunologic↗
PubMed1977

Results with methyl-CCNU and DTIC in metastatic melanoma.

This report is the result of an Eastern Cooperative Oncology Group (ECOG) study. Four hundred and 15 patients with inoperable metastatic malignant melanoma, excluding those with cutaneous metastases only, were randomized to one of three drug treatments: DTIC alone, methyl-CCNU alone, or the combination DTIC plus methyl-CCNU. Responses were seen in 14% of DTIC patients (19/127), 15% of methyl-CCNU patients (18/119) and 14% of DTIC plus methyl-CCNU patients (18/122). Duration of response was the same (14 weeks) for all three treatment groups. There was no difference among the treatments in achieving complete responses. Survival was improved significantly for responders (50 weeks) compared with nonresponders (15 weeks) regardless of treatment regimen. Toxicities were generally tolerable. DTIC caused significantly more gastrointestinal toxicity than methyl-CCNU. Methyl-CCNU caused significantly more bone marrow toxicity than DTIC. There were three drug-related deaths. All occurred in patients on combination DTIC plus methyl-CCNU. Important pretreatment characteristics that favor response are ambulatory status, female, less than 50 years old, no prior chemotherapy and no liver or brain metastases. Patients with favorable characteristics combinations had a 30% response rate, while those with unfavorable characteristic combinations had only a 9% response rate.

Brain Neoplasms↗
PubMed1976

Familial colon cancer.

Study was made of a kindred with a strong history of carcinoma of the colon. Twenty-three family members were screened for the tumor with carcinoembryonic antigen (CEA) assay, barium enema, and proctoscopy; one occult colon cancer was diagnosed. Identification and surveillance of families at high colon cancer was diagnosed. Identification and surveillance of families at high risk of cancer can provide unusual opportunities for early tumor detection.

Adenocarcinoma↗
PubMed1976

Results of a randomized study comparing DTIC with TIC mustard in malignant melanoma.

This prospective randomized Eastern Cooperative Oncology Group (ECOG) study (1071) was designed to compare a new and promising cytotoxic agent TIC Mustard (triazeno imidazole carboxamide mustard, NSC 82196) with DTIC (dimethyl triazeno imidazole carboxamide, NSC 45388) in the treatment of inoperable melanoma. One hundred and seventy-eight patients were randomized to receive either DTIC (150 mg/m2/day X 5) or TIC Mustard (800 mg/m2/day X 5). Of this group 145 patients were evaluable for tumor response at the completion of the study. Objective responses were seen in 15/79 (19.0%) DTIC patients and 4/66 (6.1%) TIC Mustard patients. Adjustment of crude response rates yielded final response rates of 18.2% for DTIC patients and 5.8% for TIC Mustard. These differences were significant at the p less than or equal to .03 level. Median response duration was 15 weeks for the DTIC responders and 4 weeks for the TIC Mustard responders. Responders and nonresponders did not differ significantly in any of the standard prognostic categories. However, responders had a significantly longer median survival (47.5 weeks) compared to that for nonresponders (17.8 weeks). Toxicity was tolerable for either drug and no deaths were ascribed to either. We conclude that TIC Mustard has limited usefulness in the treatment of malignant melanoma and is less effective than DTIC.

Clinical Trials as Topic↗
PubMed1976

Streptozocin-treated Verner-Morrison Syndrome: plasma vasoactive intestinal peptide and tumor responses.

A patient with watery diarrhea, hypokalemia, hypochlorhydria, and a non-beta islet cell carcinoma of the pancreas (Verner-Morrison syndrome) was found to have an elevated vasoactive intestinal peptide (VIP) concentration in the plasma as well as in the tumor. Treatment with streptozocin resulted in a dramatic subjective and objective tumor response in this patient. Plasma VIP concentration fell into the normal range after four courses of treatment, diarrhea ceased after the third course of therapy, and measurable tumor mass markedly decreased during that same period of time. The patient remains in clinical remission with no evidence of tumor regrowth 18 months after the beginning of treatment. In this patient, plasma VIP measurements were an excellent marker of tumor activity and correlated well with objective disease measurements and clinical response.

Adenoma, Islet Cell↗
PubMed1975

Selective and non-selective lymphocytotoxicity in human melanoma: observation on the effect of long-term culture and fetal bovine serum on target-cell sensitivity to lymphocytes.

In vitro cell mediated cytotoxicity (CMC) assays have been conducted in a human melanoma system with a 3H-proline retention technique. Melanoma target cells from long-term cultures ("cell lines") are found to exhibit increased susceptibility for lymphocyte cytotoxicity in comparison to the same target cells from short-term culture. The higher sensitivity of the "cell line" derived target cells is seen with lymphocytes, irrespective of diagnosis of the donor. In parallel experiments with the target cells grown in medium supplemented with fetal calf serum (FCS) and AB+ human serum (from a normal male doner), the melanoma target cells grown with FCS do not show any enhanced cytotoxicity, suggesting no causal relationship of such enhanced sensitivity of "cell line"-derived target cells to "heterologous melanoma antigens" that might have been acquired by the target cells following the use of FCS in tissue culture. In controlled assays of in vitro CMC, lymphocytes from melanoma patients (14/44) exhibited selective cytotoxicity (destruction of only one target-cell type) against the melanoma target cells, whereas only 3/97 control lymphocytes (other malignancies and normal donors) showed such melanoma-selective cytotoxicity. This difference is statistically significant at p less than 0.001. Non-selective cytotoxicity (destruction of two or more unrelated target cell types) was seen with lymphocytes from 9/44 melanoma patients, 13/51 patients with other malignancies and 8/46 normal donors. No correlation of selective cytotoxicity could be established with donors' age, sex, stage of disease, therapy or history of blood transfusion. Such a correlation may emerge as our series becomes larger. Despite the lack of any correlation between selective cytotoxicity and disease status, our study reaffirms the existence of selective cytotoxicity by melanoma patients' lymphocytes against melanoma target cells.

Animals↗
PubMed1975

Variables and specificity of in vitro lymphocyte-mediated cytotoxicity in human melanoma.

In vitro cell-mediated cytotoxicity (CMC) assays have been carried out in human melanoma system with blood effector lymphocytes on [3H]proline-labeled target cells in a 48-hr microcytotoxicity technique. Three lymphocyte purification procedures (Ficoll:Hypaque gradient, plasma gel sedimentation followed by nylon column incubation, and plasma gel sedimentation followed by separation with nylon powder and glass beads) are compared in parallel experiments for characteristic effector cell composition and cytotoxic potential against target cells of dissimilar histology. The cytotoxicity is defined by the loss of target cell 3H cpm as measured by residual target cell 3H cpm in individual microwell following incubation with lymphocytes. Target cell 3H cpm loss by test lymphocytes is compared with target cell 3H cpm loss by several age and sex matched control lymphocytes (from normal donors and unrelated cancer patients); further comparison between the various control lymphocytes is also made in each assay. As control for target cells, autologous fibroblasts and homologous tumor cells of dissimilar histology are always included in each assay. Specific cytotoxicity is defined as statistically significant and selective destruction of only melanoma cells by the test lymphocytes as compared to the control lymphocytes. Significant but nonselective destruction of 2 or more target cells of unrelated histology is regarded as nonspecific cytotoxicity, while no destruction of any target cells signifies no cytotoxicity. The Ficoll:Hypaque preparations consistently exhibit the highest nonlymphocytic cell contamination (8 to 16%); the nonlymphocytic cells are, almost exclusively, monocytes. They also produce relatively high percentage of thymus independent (B) cells (8 to 15%). The ultimate cell composition of the 2 plasma gel-nylon preparations is essentially identical. In either plasma gel-nylon preparations, the nonlymphocytic contamination is minimal (0 to 4%) and thymus-dependent (T) cell percentage is considerably higher (92 to 99%) with none or few B cells.

Cell Separation↗