PubMed Health⌕ Search

Biomedical subjects

C N Sternberg

Publications and source records attributed to C N Sternberg.

At least 73 records · Page 4Linked to original sources
PubMed1988

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) effect on the primary bladder lesion.

Of 50 patients with bladder cancer given 1 to 5 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin in a pilot phase I and II study 63 per cent of 41 with pure transitional cell stage T2-4 lesions responded. While significant downstaging occurred by transurethral resection of the bladder in 70 per cent and by cytology in 60 per cent of the patients, the final T response rate by all noninvasive clinical staging procedures, including sonography and computerized tomography, revealed complete remission in 24 per cent and partial remission in 39 per cent. Of 30 patients who underwent pathological staging 33 per cent achieved stage P0 and 17 per cent stage Tis disease or P less than T. Despite extensive re-evaluation by transurethral resection of the bladder and other noninvasive staging procedures, a clinical staging error (T versus P) of 38 per cent was observed. Of the other 9 patients 4 with mixed nontransitional cell histological findings at presentation never achieved complete remission, although 3 had resolution of all transitional cell elements and 5 (10 per cent) were inevaluable. The toxicity of the regimen was generally acceptable but 6 per cent of the patients required hospitalization for neutropenic fever. While this active regimen can clinically (T) and pathologically (P) induce downstaging in a significant number of patients with primary bladder tumors, this pilot study has raised serious questions concerning the design of future nonrandomized and randomized neoadjuvant studies.

Adult↗
PubMed1988

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for extravesical urinary tract tumors.

A total of 11 patients with stage T2-4N0M0 extravesical tumors (prostate, prostatic urethra, urethra and ureter) received 1 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin. Of 10 evaluable patients 4 (40 per cent) had downstaging to T0 disease with a clinical complete remission observed in 3 of 5 (60 per cent) with transitional cell tumors of the prostate and prostatic urethra. Four patients with urethral tumors of mixed or nontransitional histology failed to achieve a complete remission. The disease was staged pathologically in 4 patients: 1 had a partial remission and 3 had progression (all 4 had residual disease). Because therapy with methotrexate, vinblastine, doxorubicin and cisplatin induced only significant tumor regression of transitional cell elements of extravesical tumors and because it was ineffective against mixed histological tumors and in preventing new stage Tis lesions, surgical resection of such lesions is required.

Aged↗
PubMed1988

Etoposide (VP-16) in the treatment of advanced adenocarcinoma of the pancreas.

Twenty-six patients with advanced adenocarcinoma of the pancreas were treated with etoposide (VP-16), 100-180 mg/m2 i.v., days 1, 2, and 3, monthly. Twenty-five had bidimensionally measurable disease and one had evaluable disease only. This regimen and dosage schedule were well tolerated, with minimal toxicity including myelosuppression; a median WBC count nadir of 3,600 cells/mm3 (range 200-2,400); and a median platelet nadir of 215,000 cells/mm3 (range 15,000-405,000). However, no patients responded and only two had stable disease for 3.5 and 4 months, respectively. At this dosage and schedule, there is no role for VP-16 in the treatment of advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1988

Phase II trial of menogarol in the treatment of advanced adenocarcinoma of the pancreas.

Fifteen patients with advanced adenocarcinoma of the pancreas were treated with menogarol 150-225 mg/m2 i.v. every 3 weeks. All patients had bidimensionally measurable disease. This regimen and dosage schedule are well tolerated, with minimal toxicity that included myelosupression; median white blood cell (WBC) count nadir of 2,700 cells/mm3 (range 1,400-7,100 cells/mm3) and median platelet nadir of 162,000 cells/mm3 (range 53,000-390,000 cells/mm3). Anorexia occurred in one patient, nausea or vomiting in six, phlebitis in one, and alopecia in six patients. No patients responded. At this dosage and schedule, there is no role for menogarol in the treatment of advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1987

Evaluation of new anticancer agents against human pancreatic carcinomas in nude mice.

Heterotransplantation of human cancers in nude mice has provided an in vivo model for studying the biologic characteristics of human tumors, particularly their response to chemotherapy. In an effort to identify cytotoxic agents effective against pancreatic carcinoma, this model was used to evaluate the efficacy of three new anticancer agents--menogarol, 4'-epirubicin, and taxol--against two human transplanted pancreatic tumors. Relative area (tumor length X width) differed significantly between menogarol-treated and control groups (p = 0.034). A marked response was also observed in the tumors to 4'-epirubicin (p = 0.01). Taxol was ineffective in controlling tumor growth; by the fourth week, the size of treated tumors was similar to that of the control group (p = 0.55). No toxicity was observed in either the menogarol- or taxol-treated animals. Animals bearing the P2 tumor, and treated with 4' epirubicin displayed severe toxicity by day 18 with death by day 21 in most animals. For the second tumor, Capan-1, relative area differed significantly between the menogarol-treated and the control group (p = 0.003). In animals given 4'-epirubicin, a smaller difference was observed when comparing the relative areas (p = 0.09). Animals treated with taxol again showed no difference in the tumors when compared with controls (p = 1.0). The use of the nude mouse system has evolved so that tumor-oriented trials are now feasible with the hope of clinical applicability. This study illustrates that at least two agents--menogarol and 4'-epirubicin--may have some antitumor activity against pancreatic carcinoma in this system.

Adult↗
PubMed1987

Current status of chemotherapy for urothelial tract tumors.

The standard therapy for muscle-infiltrating tumors of the bladder remains radical cystectomy with or without radiation. Caution should be exercised about recommending newer regimens outside of clinical trials. However, combination chemotherapy programs can produce dramatic and durable remissions in a significant percentage of patients with advanced urothelial tract malignancies.

Antineoplastic Agents↗
PubMed1987

Advances in the treatment of urothelial tract tumors.

Recently developed combination chemotherapy programs have now produced durable complete remissions in a significant percentage of patients with advanced urothelial tract malignancies. For advanced disease, efforts must still be directed at developing new agents but must also focus on understanding drug resistance. Some tumors appear to be resistant de novo; others respond for a period of time before a resistant population emerges. Clearly multiple factors come into play. In some cases, pharmacologic factors such as bioavailability metabolism, or toxicities predominate. In other cases, specific genes expressing surface proteins such as the p-glycoprotein identified in resistant ovarian tumors have been implicated. In the 1980s, it is no longer adequate to define tumors simply by pathologic inspection. As demonstrated by Russell and co-workers xenografts of phenotypically similar transitional cell tumors in nude mice demonstrated marked heterogeneity with respect to flow cytometric DNA analysis and immunocytochemistry. With the recent adoption of flow cytometric techniques, both from bladder washings and paraffin sections, insight into the biologic behavior of individual tumors may soon be possible. Blood group antigen expression and monoclonal antibodies to tumor-associated antigens may also help in this regard. For primary tumors, attention is now being focused on protocols aimed at bladder preservation. In some cases, radiation therapy alone can produce long-term survival, despite muscle infiltrating disease. Complete remissions have also been described with chemotherapy alone. The interaction of chemotherapy and radiation therapy has only recently begun to be investigated. In these trials, complete local control must still be the primary goal. Standard criteria for staging and response evaluation, including pathologic documentation of remission status, are crucial. To demonstrate a beneficial effect of therapy, long-term randomized trials will be required. The goal of individualized therapies may soon be possible, which will ideally translate into increased clinical benefit for patients with urothelial tract tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Phase I/II trial of intravesical methotrexate for superficial bladder tumors.

Twenty-one patients with superficial transitional cell carcinoma of the bladder received a total of 121 doses of intravesical methotrexate (MTX) at 11 different concentrations of drug, ranging from 40 mg/m2 (mean concentration of 2.9 X 10(-3) M) to 500 mg/m2 (4.9 X 10(-2) M). Biochemical evidence of absorption was minimal in all cases. The maximum serum level was observed within 0.5-2 h in all patients and ranged from 1.8 X 10(-8) M to 5.0 X 10(-7) M. By 24 h the serum levels were negligible and ranged from 5.5 X 10(-9) M (the lowest limit detectable by the assay) to 4.4 X 10(-8) M in the patient who received the highest dosage of 500 mg/m2. Biologic evidence of absorption was minimal. Myelosuppression, mucositis, and nausea were not observed. Eighteen patients received six consecutive weekly doses ranging from 40 to 500 mg/m2. All patients had repeat cytoscopy performed within 2-4 weeks after six consecutive doses to evaluate local toxicity and efficacy. Flow cytometry was performed on the bladder washings of 22 patients, illustrating the use of flow cytometry, in conjunction with conventional cytology, as an additional means of objectively quantifying results. Despite MTX's established activity in systemic treatment of advanced bladder carcinoma, this study failed to demonstrate any clinical response to intravesically administered MTX, in doses of up to 500 mg/m2, and in concentrations of up to 4.9 X 10(-2) M.

Adult↗
PubMed1986

Morphological, biological, biochemical, and karyotypic characteristics of human pancreatic ductal adenocarcinoma Capan-2 in tissue culture and the nude mouse.

Human pancreatic ductal adenocarcinoma Capan-2, derived from a 56-yr-old male Caucasian, has been studied in both tissue culture and the nude mouse. In tissue culture, tumor cells showed epithelial-like features, whereas in the nude mouse, the tumor grew as a well-differentiated adenocarcinoma, resembling histopathologically the original neoplasm. Ultrastructurally, the neoplastic cells showed characteristics of ductal epithelium. The allozyme phenotypic profile of Tumor Capan-2 was determined in eight genetically determined loci, and chromosome studies showed a hypotetraploid pattern with a number of morphological and numerical changes. Carcinoembryonic antigen was produced in trace amounts, and lactate dehydrogenase was represented only by Isoenzyme 5, regardless of environmental conditions. The characteristics of Capan-2 tumor make it a valuable addition to the small number of available pancreatic tumor lines in studies aiming at clarifying certain aspects of the biology of this type of malignancy.

Animals↗
PubMed1985

Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium.

The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases.

Adult↗