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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 199 records · Page 11Linked to original sources
PubMed1984

Chemotherapy of advanced colorectal carcinoma: fluorouracil alone vs. two drug combinations using fluorouracil, hydroxyurea, semustine, dacarbazine, razoxane, and mitomycin. A phase III trial by the Eastern Cooperative Oncology Group (EST: 1278).

Patients with advanced colorectal cancer and no prior chemotherapy were randomized to six treatment regimens: A) fluorouracil (FU) alone; B) FU + hydroxyurea (HU); C) semustine (SE) + dacarbazine (DA); D) FU + HU alternating with SE + DA; E) SE + razoxane (RA); F) mitomycin (MI) + DA. There were no significant treatment differences with respect to response, which ranged from 9-23% (overall 32/207 or 15%) or median survival duration, which ranged from 17 weeks to 32 weeks. Patients treated with FU or FU + HU experienced substantially less toxicity than those on the other treatment arms.

Adenocarcinoma↗
PubMed1984

Regional intra-arterial mitomycin C infusion in previously treated patients with metastatic colorectal cancer and concomitant measurement of serum drug level.

Fifty-seven patients with unresectable metastatic colorectal cancer, after failing all conventional chemotherapy, were treated with mitomycin C (MMC) regional intra-arterial infusion. The regional artery (eg, hypogastric, hepatic, etc) was approached percutaneously via the femoral artery and MMC at a dose of 20 mg/m2 in 100 ml of 5% dextrose in water was infused for a 1-hour period; treatment was repeated every 6-8 weeks. Of 51 evaluable patients, five had objective response (three with pelvic tumor, one with liver and lung tumors, and one with liver tumors), 28 had stabilization of tumor, and 18 had no response. Median survival times for the responders, stabilized patients, and nonresponders were 46+, 39, and 22 weeks, respectively, with an overall survival of 32 weeks. The major side effect was necrotizing cellulitis occurring in the buttock following the pelvic infusion. Myelosuppression was manageable and other toxic effects were mild. Using the high-performance liquid chromatography method (total of 25 measurements), the average MMC levels in the peripheral circulation were 205, 62.4, and 16.0 ng/ml, respectively, immediately after injection and 1 and 2 hours following intra-arterial infusion. By 4 hours, no MMC could be detected in the peripheral circulation.

Adenocarcinoma↗
PubMed1983

Disposition of orally administered 14C-prednimustine in cancer patients.

A single oral solution dose (40 mg/m2) of 14C-prednimustine was administered to each of four cancer patients. Plasma, urine, and feces were collected at appropriate times and analyzed for total radioactivity. Plasma samples were analyzed for prednimustine. Peak plasma levels of radioactivity (1-3 micrograms 14C-prednimustine equivalents) occurred at 1.5-3 h in three patients and at 5-6 h in one patient. No intact prednimustine was detected in the plasma; this means that if present, it would be at a concentration of 0.02 micrograms/ml or less and would account for less than 1% of the total drug-related material at the time of peak plasma levels. Solvent-extractable metabolites had a plasma half-life of about 8 h or less. By 24 h essentially all the plasma radioactivity appeared to be covalently bound, and it was eliminated slowly with an estimated terminal elimination half-life of about 10 days. Rapid urinary excretion occurred in the first 24 h, and 40%-60% of the dose was recovered in the urine in 72 h. Although prednimustine was well absorbed, the ester was subject to extensive presystemic metabolism and was not present in the systemic circulation after oral administration.

Adenocarcinoma↗
PubMed1983

Adenocarcinoma of the colon masquerading as primary ovarian neoplasia. An analysis of ten cases.

This paper reviews the clinical characteristics of a group of patients in whom unsuspected primary adenocarcinoma of the colon presented with signs and symptoms of a primary ovarian neoplasia. In most patients, the ovaries were removed, the correct diagnosis was established at a later time, and a second surgery for resection of the primary adenocarcinoma of the colon was then performed. Preoperative use of colonoscopy or barium-enema examination would have helped. We compared these patients to a group of patients with similar clinical characteristics, but in whom the ovarian metastases were clinically apparent months after the resection of a primary colorectal cancer. We found that, in both groups, age of the patients, anatomic distribution of the primary tumor, histologic differentiation, serosal or mesenteric lymph node tumor involvement, and timing of the oophorectomy in relationship to removal of the primary colorectal tumor did not affect the overall survival. Once ovarian metastases were documented, patients died regardless of treatment, approximately 16 1/2 months after the diagnosis.

Adenocarcinoma↗
PubMed1983

Analysis of T cell subsets in cancer patients treated with interferon.

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Combination chemotherapy containing semustine (MeCCNU) in patients with advanced colorectal cancer previously treated with 5-fluorouracil (5-Fu).

Two hundred thirty-two patients with advanced measurable colorectal cancer previously treated with 5-fluorouracil (5-Fu) were randomized to one of the following treatments: A) semustine (MeCCNU) plus vincristine (VCR); B) MeCCNU plus dacarbazine (DTIC); C) MeCCNU plus DTIC plus VCR; D) MeCCNU plus beta-2'-deoxythioguanosine (beta-TGdR). Platelet nadirs less than 50,000/mm3 were noted in 9% (Treatment A) to 19% (D) of the patients while WBC nadirs less than 2,000/mm3 were noted in 7% (B) to 12% (C,D) of the patients. Severe vomiting was noted in 2% (D) to 14% (B) of the patients. The partial response rates and median survival times from date of randomization were as follows: Treatment A: 3/54 (6%), 19 weeks; B: 9/59 (16%), 28 weeks; C: 3/60 (5%), 25 weeks; D: 2/59 (4%), 19 weeks. Differences in response rate and median survival are not statistically significant.

Antineoplastic Agents↗
PubMed1983

Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic colon tumors.

The secretion of plasminogen activator by explants of 92 human malignant tumors was studied in short-term organ culture. Where possible, adjacent normal tissue of the presumed origin of the tumors was also studied. The study included adenocarcinomas of the lung, colon, prostate, breast, and stomach and different types of sarcomas. In addition to the measurement of secretion rates, all tissues were quantitatively extracted to determine the amount of cell-bound enzyme. Both culture fluids and extracts were analyzed with respect to the type of plasminogen activator they contained by immunoinhibition with goat immunoglobulin G formed against purified human urinary urokinase sodium dodecyl sulfate:gel electrophoresis followed by zymography. The study yielded the following conclusions: (a) the measurement of plasminogen activator secretion rates gives a much sharper differentiation between malignant and normal tissues than does the amount of extractable enzyme; (b) the enzymes secreted in short-term organ culture are, in the great majority of the cases studied, of the urokinase type, even when a large fraction of the activator contained in the tissue is of the vascular type; (c) the secretion rates of metastatic tumors of the colon are much lower than those of the primary ones; (d) immunoperoxidase staining of tissue sections reveals that urokinase is localized predominantly in the tumor cells. The low secretion rates of metastatic tumors, probably a reflection of this property in the original cell that gave rise to the metastatic focus, could be of advantage to circulating cancer cells. Such cells would not dissolve the microthrombus thought to be essential for the arrest of cancer cells in the capillaries of target organs.

Adolescent↗
PubMed1983

Phase I study of tricyclic nucleoside phosphate.

A phase I study of tricyclic nucleoside phosphate was conducted in 20 adults with advanced cancer. Tricyclic nucleoside phosphate was given as an iv infusion over 15 minutes once every 3 weeks; the doses ranged from 25 to 350 mg/m2. Beginning at a dose of 250 mg/m2, hyperglycemia and elevation of hepatocellular enzymes were observed; at a dose of 350 mg/m2, two patients developed irreversible liver damage. Patients at all dose levels experienced reduction in serum phosphorus; reduction of serum calcium was noted only with the two highest doses. Nausea and vomiting occurred occasionally. Myelosuppression was not a prominent toxic effect. No major therapeutic responses were noted. Further clinical trials employing this schedule are probably not warranted.

Acenaphthenes↗
PubMed1983

Phase I clinical trial of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP).

cis-Dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP), a second-generation platinum complex with little or no nephrotoxicity in preclinical studies, has undergone phase I clinical testing and initial pharmacokinetic evaluation in 26 patients with solid tumors who received 40 courses of treatment. Doses of 20-350 mg/m2 were evaluated as single 2-hr infusions given every 3 weeks for two doses, with 2 L of pretreatment hydration (but no diuretics) in all but five patients. Nausea and vomiting was almost universal but was severe in only three courses. The dose-limiting toxic effect was myelosuppression, with a median wbc count nadir of 2500/mm3 and a median platelet count nadir of 32,000/mm3 at the maximum tolerated dose of 350 mg/m2. No increase in serum creatinine or decrease in creatinine clearance was seen. No pretreatment hydration was given in five of the seven patients treated at 350 mg/m2. Two cases of hypersensitivity were seen. No hearing loss was observed and no other toxic effects were noted. Plasma decay of total platinum was biexponential with a prolonged beta phase. Recovery of platinum in the urine was rapid up to 8-10 hrs and slow thereafter. Recoveries were incomplete and variable (16.5%-62% of the dose at 48 hrs).

Adult↗
PubMed1982

Surgical treatment of isolated abdominal wall metastasis in colorectal cancer.

Isolated abdominal wall recurrence, following resection of a primary large bowel adenocarcinoma, is an infrequent finding. Over a ten year period, 22 patients were submitted to en bloc resection of such localized neoplastic foci. In 13 cases, recurrent tumor was located in a previous midline or para median incision. Nine patients underwent palliative radiotherapy and/or chemotherapy once the recurrent disease was identified, and were operated on when uncontrolled progression was clinically evident. In all cases, 4-5 cm disease-free margins were obtained. In eight patients it was possible to close the defect primarily and 14 patients required marlex mesh. Twelve patients were alive at two years and ten patients at five-years follow-up mark. Mucin-producing or poorly differentiated adenocarcinoma had the worse prognosis. Synthetic prosthesis allowed for adequate resections with little morbidity and acceptable cosmesis. Symptomatic relief and long-term palliation can be achieved with aggressive surgery. The role of adjuvant chemotherapy and radiation therapy still needs to be evaluated. The aggressiveness of poorly differentiated and the mucin producing adenocarcinoma should temper radical surgical exercises.

Abdominal Muscles↗
PubMed1982

Combination chemotherapy of advanced colorectal cancer utilizing 5-fluorouracil, semustine, dacarbazine, vincristine, and hydroxyurea: a phase III trial by the Eastern Cooperative Oncology Group (EST: 4275).

Patients who had measurable evidence of recurrent or metastatic colorectal carcinoma following surgery and radiotherapy but no prior chemotherapy were randomized to one of five combination chemotherapy programs. Four of the treatments utilized five consecutive days of fluorouracil (FU) (days 1--5 and days 36--40) plus one oral dose of semustine (ME) (day 1) every ten weeks: (A) FU + ME; (B) FU + ME + vincristine (VC) (day 1 and day 36); (C) FU + ME + dacarbazine (DC) (days 1, 2, 36, 37); (D) FU + ME + VC + DC. The fifth treatment option(E) used a weekly treatment program of FU I.V. on day 1 plus hydroxyurea (HU) P.O. on day 4. The overall response rate was 13% (60/472) and the median survival time from start of therapy for all patients was 31 weeks. The response rate and the median survival time for each combination was (A) 9/103 = 9%, 26 weeks; (B) 10/92 = 11%, 28 weeks; (C) 15/101 = 15%, 37 weeks; (D) 11/91 = 12%, 27 weeks; (E) 15/85 = 18%, 38 weeks. There is no statistical difference in response rate or survival duration among any of the treatment options. The therapies containing DC produced the only complete responses (3 patients on treatment C and 2 on D). Treatment D was also associated with the longest median response duration (Treatment D = 55 weeks). Treatment A (FU + ME) was associated with the highest incidence of life-threatening toxicity.

Antineoplastic Agents↗
PubMed1982

Mesothelial cysts associated with metastases to ovary from primary colonic carcinoma.

The three cases herein reported concern metachronous ovarian metastases from primary adenocarcinomas of the colon associated with mesothelial cysts. Although the etiology of these cysts remains obscure, the cases were of interest because the cysts did not contain tumor cells despite the intimate relationship to the tumor. Metastases were localized to the ovary and were resectable. All signs and symptoms disappeared, affording excellent palliation and an extended survival.

Adenocarcinoma↗
PubMed1982

Management and survival of adenocarcinoma of the rectum in the United States: results of a national survey by the American College of Surgeons.

Data from the long- and short-term surveys of the American College of Surgeons Commission on Cancer were examined to evaluate the survival and management of patients with rectal cancer in the United States. Overall, females experienced better survival than males, and white had better survival than blacks. The 5-year survival rates for localized, regional and distant stages of the disease were 76.4, 43.1, and 5.5% respectively. The survival rates in relation to histologic grade of the tumor indicated that the survival experiences of patients with well and moderately differentiated tumors were similar (57% versus 54%) and that patients with poorly differentiated tumors had significantly lower survival (35%). The survival experience of those receiving abdominoperineal resection was similar to those treated by low anterior resection (56% versus 58%). Location of the tumor in the rectum did not affect prognosis.

Adenocarcinoma↗
PubMed1982

Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in treatment of colorectal carcinomas.

The effects of thymidine (dThd) coadministration on the pharmacokinetics and metabolism of 5-fluorouracil (FUra) were investigated in 29 colorectal cancer patients. Five patients received 5-day i.v. infusion of FUra at 15 mg/kg/day and 24 patients received infusion of FUra (7.5 mg/kg/day, 5 days) and dThd (216 mg/kg/day, 6 days) preceded by a bolus dose of dThd (405 mg/kg). Plasma and urine concentrations of FUra, 5-fluorodeoxyuridine (FdUrd), thymine, and dThd were quantitated by a high-pressure liquid chromatographic assay. Concurrent dThd administration reduced the plasma clearance of FUra at steady state from 389.1 +/- 153.5 (S.D.) to 56.0 +/- 36.4 liters/kg/day. The mean steady-state plasma concentration of FUra in patients receiving FUra alone was 0.38 microM and was significantly lower than the 1.30 microM in patients receiving FUra-dThd. Plasma concentrations of FUra were linearly dependent on those of thymine. Furthermore, the metabolic and renal clearances of FUra decreased inversely with thymine concentrations indicating that the elimination of FUra was reduced by thymine. In contrast to the absence of FdUrd as a circulating metabolite in patients treated with FUra alone, microM concentrations of FdUrd were detected in plasma of most of the patients treated with FUra-dThd. This together with the linear correlation of FdUrd and dThd concentrations indicates that the interconversion of FUra to FdUrd was enhanced by dThd. The incidence of dose-limiting leukopenia in the FUra-dThd combination therapy was 40%. There is an inverse correlation between the plasma clearance of FUra at steady state and hematological toxicity. The plasma clearance of FUra in the toxic population was 32.0 +/- 16.8 liters/kg/day and was significantly lower than the clearance of 72.0 +/- 37.3 liters/kg/day in the nontoxic population (p less than 0.001). The corresponding critical toxic steady-state FUra plasma concentration was 1.5 microM. The biochemical effects of dThd on the incorporation of FUra and FdUrd into RNA and into acid-soluble 5-fluorodeoxyuridine monophosphate (FdUMP) in human colon tumor cells were studied in vitro. At 100 microM, dThd increased the incorporation of FUra into RNA up to 4-fold but diminished the acid-soluble FdUMP pool. Similarly, the incorporation of FdUrd into acid-soluble FdUMP was inhibited by dThd. The response rate of colorectal carcinoma to FUra was not improved by coadministration of dThd; only one of the 11 patients who had no prior FUra therapy achieved partial remission. The lack of clinical response in these patients may be partly due to the inhibition of anabolism of FUra and FdUrd to FdUMP by dThd.

Colonic Neoplasms↗