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Biomedical subjects

R C Watson

Publications and source records attributed to R C Watson.

At least 37 records · Page 2Linked to original sources
PubMed1986

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer.

Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30-37.5 mg/m2 IV QW. In responding patients drug was given QOW after 4-6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m2 depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.

Aged↗
PubMed1986

Etoposide in prostatic cancer: experimental studies and phase II trial in patients with bidimensionally measurable disease.

Etoposide, a semisynthetic derivative of podophyllotoxin, was evaluated concurrently in vitro against a human derived hormone-resistant cell line, PC-3, and in vivo in bidimensionally measurable hormone-resistant human prostatic cancer. In vitro, a dose-response relationship was observed, with 74% inhibition at 10 micrograms/ml (1 h incubation) and greater than 99% inhibition at 90 micrograms/ml, both in the range of clinically achievable concentrations. In vivo, 1 PR (5%, 95% confidence limits 0-12%) of 18+ months was observed in 20 adequately treated patients. The results confirm the limited role of etoposide in hormone-refractory disease and the need for new model systems for evaluation of potential chemotherapeutic compounds in this disease.

Adenocarcinoma↗
PubMed1986

Selection of testicular tumor patients for omission of retroperitoneal lymph node dissection.

Excluding patients with bulky stages II or III disease, 73 patients with nonseminomatous germ cell testicular tumors were evaluated between September 1979 and April 1983 for a protocol omitting retroperitoneal lymph node dissection. Patient eligibility required clinical stage I (T1 category) disease based upon normal post-orchiectomy serum tumor markers (alpha-fetoprotein, human chorionic gonadotropin and lactic dehydrogenase), chest x-ray, ipsilateral lymphangiography, and a computerized tomography scan of the abdomen and pelvis. Of the 73 patients 10 (14 per cent) were entered and followed for more than 2 years (3 had relapse within 7 months but were salvaged with retroperitoneal lymph node dissection and chemotherapy). Analysis of failures showed embryonal carcinoma in all 3 patients, with vascular invasion in the primary tumor in 1 and undetected spermatic cord involvement in 1, while 1 had a slower than expected decrease to normal of an elevated human chorionic gonadotropin level after orchiectomy. There were 63 patients (86 per cent) excluded from the protocol for various reasons: 2 (3 per cent) refused treatment, 16 (25 per cent) had suspicious or positive lymphangiography, 22 (40 per cent) had a positive CT scan, 6 (9 per cent) had elevated tumor markers, 3 (5 per cent) were less than 15 or more than 15 or more than 40 years old, 8 (13 per cent) had had a prior orchiopexy or scrotal violation, 4 (6 per cent) had extension to the spermatic cord and 2 (3 per cent) were unavailable for monthly followup. These 63 patients underwent retroperitoneal lymph node dissection, and 36 (57 per cent) had negative and 27 (43 per cent) had positive nodes (8 had stage N1, 10 stage N2A, 6 stage N2B and 3 stage N3 disease). Average interval from orchiectomy to final staging was 6 weeks. The results suggest that assessment of local tumor extent and potential sites of metastases via all available means are necessary in an effort to reduce the risk of tumor recurrence in patients who are followed expectantly.

Adolescent↗
PubMed1986

Transthoracic aspiration cytology of pulmonary lesions.

In a seven-year period (1974 to 1981), 1,390 patients had transthoracic aspiration biopsy for radiologically suspected pulmonary neoplasms. Of the 1,209 proven malignant neoplasms, 1,059 (88%) were cytologically diagnosed as malignant. There were only two (0.2%) false-positive diagnoses both due to florid bronchoalveolar hyperplasia associated with granulomatous disease. Cytologic and histologic correlations for primary lung cancers were 92% for adenocarcinoma, 87% for oat cell (small cell) carcinoma, and 83% for epidermoid carcinoma. Characteristic cytomorphology of pulmonary carcinomas, some metastatic neoplasms, and inflammatory lesions are described.

Adenocarcinoma↗
PubMed1986

Application of active recovery techniques for a simulated ice hockey task.

Three, 15 minute recovery modes between two maximal effort, intermittent work bouts were tested using eight male hockey players (21.9 +/- 1.4 yrs.). The work bouts were comprised of six, 45 second skating trials, each interspersed with 90 seconds of rest. Performance scores were based on average distance skated/trial. Changes in lactate concentrations were determined from venous samples obtained at rest, prior to and following the recovery mode. Bench-stepping during recovery resulted in significantly lower lactates (6.1 +/- 2.2 mmol . 1-1) than for rest recovery (8.1 +/- 1.6 mmol . 1-1), while skating recovery was not significantly different from either bench-stepping or rest. Subsequent performance (WB2) was significantly lower than initial performance (WB1) for all treatments and it was unrelated to differing post-recovery lactate concentrations. It was concluded that bench-stepping enhanced lactate removal but subsequent performance was unaffected by any treatment.

Adult↗
PubMed1986

Laboratory and on-ice test comparisons of anaerobic power of ice hockey players.

The suitability of the Wingate Anaerobic Test (WAT40) as a laboratory measure of anaerobic capacity (AnCap) and power (AnPow) of ice hockey players was tested against the Reed Repeat Sprint Skate-RSS (1979) and the Sargeant Anaerobic Skate (SAS40). Twenty-four university and Junior A players (20.2 +/- 1.6 years), assigned by random draw, performed the three tests over a seven day period. Blood lactate taken from an unwarmed finger tip was used to assess work intensity. The AnCap (7.7 +/- 0.2 Watts X kg-1) and AnPow (10.1 +/- 0.2 Watts X kg-1) for WAT40 were significantly lower (p less than 0.05) than for RSS (AnCap 9.3 +/- 0.8 Watts X kg-1; AnPow 11.5 +/- 1.1 Watts X kg-1) and SAS40 (AnCap 9.7 +/- 0.8 Watts X kg-1; AnPow 11.9 +/- 1.8 Watts X kg-1). SAS40 was significantly higher (p less than 0.05) than RSS for both AnCap and AnPow. The RSS (r = 0.96; ME 4.5%) and SAS40 (r = 0.97; ME = 3.6%) showed excellent test-retest reliability and reproducibility for AnCap but were only fair on AnPow (RSS: r = 0.73; ME = 10.7%; SAS40: r = 0.65; ME = 18.4%). While the correlations among the tests (AnCap: SAS40 vs WAT40, r = 0.73; RSS vs WAT40, r = 0.69) were significant (p less than 0.05), the highest predictive capability estimate (r2) was only 53.3%. The correlations for blood lactates (WAT40: 10.8 +/- 1.5 mmol X l-1; SAS40: 10.7 +/- 1.9 mmol X l-1; RSS: 11.5 +/- 1.6 mmol X l-1) were not significant. Based upon the particular protocol used, the laboratory test WAT40 does not demonstrate a high relationship with on-ice measures of AnCap and AnPow in this group of ice hockey players.

Adolescent↗
PubMed1985

Phase-II trial of 4-demethoxydaunorubicin (DMDR) for advanced hypernephroma.

A phase-II trial of 4-demethoxydaunorubicin (4-DMDR) was performed in 21 patients with advanced renal cell carcinoma. The drug had demonstrated a broader spectrum of activity with less cardiotoxicity in preclinical evaluation than the parent compound daunorubicin. The starting dose was 12.5 mg/m2, with escalations to 15 and 17.5 mg/m2 in the absence of toxicity. Myelosuppression was the primary toxicity and cardiac toxicity was not seen in four patients who received four or more doses of DMDR. No responses were seen in 19 adequately treated patients, including 14 who had received no prior therapy.

Aged↗
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↗
PubMed1985

Vinblastine and methotrexate for advanced bladder cancer.

Fifty-seven patients with advanced measurable urothelial tract cancer, 52 of whom had an adequate trial, were treated weekly with 3 to 4 mg. per m.2 vinblastine and 30 to 40 mg. per m.2 methotrexate. Of 3 patients with unidimensional parameters 2 showed improvement lasting 16 and 27 months, which was documented by serial cystoscopic examinations. An additional 2 patients had measurable disease that could have been encompassed in a preoperative radiotherapy field. Both patients are free of disease at more than 12 and 14 months, respectively. Of the 47 patients with bidimensionally measurable parameters 19 (40 per cent) achieved a complete or partial remission lasting a median of 8 months, with a range of 1 to 24 months. Of 25 patients with intra-abdominal or pelvic disease 7 achieved a complete or partial remission and 5 also had a minor remission. Of note, 18 of 38 patients who had received no prior chemotherapy achieved a remission versus 1 of 9 who had been treated previously (p equals 0.06). Responders frequently obtained another remission with subsequent chemotherapy (4 of 9 versus 0 of 16, p equals 0.03). Responders lived 14 months versus 8 months for nonresponders (p equals 0.02). Four responders had brain metastases compared to none of 28 nonresponders. The combination of vinblastine and methotrexate is a well tolerated, effective outpatient regimen for patients with urothelial tract cancers.

Adult↗
PubMed1985

Carcinomatous involvement of the hilum and mediastinum: computed tomographic and magnetic resonance evaluation.

Magnetic resonance (MR) imaging and computed tomography (CT) were compared in 20 patients who had primary lung tumors, and the results were correlated with findings at surgery and pathologic evaluation. Both studies demonstrated a similar ability to detect hilar and mediastinal tumor. MR imaging detected more enlarged nodes in the mediastinum, but in several patients these enlarged nodes did not contain tumor. Consequently, MR imaging has a slightly higher false-positive rate in the evaluation of the mediastinum. Both modalities were highly sensitive, with specificity limited by the presence of enlarged benign lymph nodes in this series of patients.

Adenocarcinoma↗
PubMed1985

Cholangitis complicating intraarterial chemotherapy in liver metastasis.

In the past 2 years at our institution, 87 patients with hepatic metastasis from colorectal carcinoma have undergone surgical implantation of an arterial pump for the direct infusion of chemotherapeutic agents into the liver. We report six cases of cholangitis complicating the course of these patients.

Alkaline Phosphatase↗
PubMed1985

Methylglyoxal-bis(guanylhydrazone) in hormone-resistant adenocarcinoma of the prostate.

Methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of polyamine synthesis, was administered to 35 patients with hormone-resistant advanced adenocarcinoma of the prostate in doses of 500 or 600 mg/m2 per week intravenously. Of 31 patients with bidimensional measurable soft-tissue lesions, 25 had an adequate trial, defined as four or more doses. Six (24%; 95% confidence limits, 8% to 32%) patients achieved a partial remission (greater than or equal to 50% reduction in tumor size) in soft-tissue disease. Response was noted to start after one to two doses and persisted for a median of three months (range, 1 to 4 months). Toxicity was tolerable, and significant myelosuppression was not observed. The lack of response in osseous metastases may be secondary to the short duration of remission or to the presence or inducibility of the enzyme ornithine decarboxylase in bone. Since some animal prostatic cancer tumor models are sensitive to cytotoxic drugs that produce polyamine inhibition, clinical trials of MGBG combined with other inhibitors of the polyamine pathway should be explored.

Adenocarcinoma↗
PubMed1984

Estrogen, progesterone, and androgen-binding sites in renal cell carcinoma. Observations obtained in Phase II trial of flutamide.

A Phase II disease-oriented drug trial using flutamide (4'-nitro-3'trifluoro-methylisobutyranilide) 250 mg by mouth three times a day was undertaken in 28 patients with advanced, bidimensionally measurable renal cell carcinoma. Of 25 adequately treated cases, 1 (4%, 95% confidence limits 0-12%) had a partial remission lasting 9+ months, and 2 had stabilization of disease lasting 6 and 15 months, respectively. Flutamide demonstrated no significant antitumor activity in patients with disseminated renal cell carcinoma. Including patients entered in this study, 62 specimens were evaluated for steroid binding sites using a fluorescent method: 33 of 62 specimens assayed showed no hormone-binding sites, and only 12 cases had androgen binding. Of the 12 of 23 patients receiving flutamide who were biopsied and had an adequate sample for steroid-binding site determination, estrogen binding was demonstrated in 6, androgen binding in 3, and progesterone binding in 4. Since this study did not obtain a sufficient number of cases with androgen-binding positivity, the possible efficacy of flutamide in such cases cannot be excluded.

Adenocarcinoma↗
PubMed1984

Splenectomy after angiographic embolization of the splenic artery in patients with massive splenomegaly and severe thrombocytopenia, in juvenile subacute myelomonocytic leukemia.

Splenectomy for massive splenomegaly in thrombocytopenic patients refractory to platelet transfusions carries increased surgical risks. Blocking of the splenic artery may reduce the size of the organ, prolong the survival of transfused platelets, and reduce the surgical complications. We describe four cases of extreme splenomegaly and thrombocytopenia where successful splenectomy was carried out after angiographic embolization of the splenic artery in children with juvenile chronic myelogenous leukemia. Significant improvement was observed in platelet counts and in the survival of platelets after transfusions in three of the patients. There was a concomitant decrease in transfusion requirements. Isoimmunization prevented prolonged platelet survival in the fourth case. We recommend earlier splenectomy in these patients to reduce transfusion requirements and delay the onset of poor platelet survival after transfusions.

Blood Transfusion↗
PubMed1984

Phase II trial of doxorubicin in bidimensionally measurable prostatic adenocarcinoma.

Intravenous doxorubicin (30 to 60 mg. per m.2 every 3 weeks) was administered to 52 patients with metastatic adenocarcinoma of the prostate, including 41 with bidimensionally measurable soft tissue lesions. Prior therapy in the measurable disease group included hormonal manipulation in 39 cases, irradiation in 39 and cytotoxic drugs in 19. In 39 of 41 adequately treated patients with soft tissue lesions only 2 (5 per cent, 95 per cent confidence limits 0 to 12 per cent) achieved a partial remission for 12 and 6 months, respectively, 3 had a minor response for 5, 4 and 3 months, respectively, and 1 had stabilization of disease for 4 months. Survival in this group was 16 months versus 5 months for patients with a mixed response and progression of disease. Of 11 patients with evaluable parameters only 1 had stabilization and 5 showed subjective improvement. Recognizing the patient selection bias and treatment schedule in this study, we believe that doxorubicin has marginal activity in soft tissue lesions in patients with advanced prostatic cancer.

Adenocarcinoma↗
PubMed1984

Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.

Adolescent↗
PubMed1983

Phase II trial of sequentially administered cisplatin, cyclophosphamide and doxorubicin for urothelial tract tumors.

A total of 32 patients with urothelial tract tumors, 31 of whom had bidimensionally measurable disease parameters, underwent sequential intravenous administration of 70 mg./m.2 cisplatin, 250 mg./m.2 cyclophosphamide and 45 mg./m.2 doxorubicin on days 1 to 3 every 3 to 4 weeks. Of these patients 28 (88 per cent) were treated adequately, including 13 (46 per cent, 95 per cent confidence limits of 28 to 64 per cent) who achieved a complete (2) or partial (11) remission. Almost all remissions occurred within 1 to 3 weeks and persisted for a median duration of 8 months (range 4 to 16 months), with 5 patients responding for 1 or more years. Responders lived significantly longer than nonresponders, with a median of 91 versus 38 weeks, respectively (p less than 0.001). The over-all response rate with this 3-drug combination was not statistically different from that which has been observed in previously untreated, selected patients given cisplatin only. When the results of the 3-drug combination (92 responses in 202 patients) are compared to those of cisplatin alone (85 responses in 255 patients) the 3-drug regimen is statistically superior (p less than 0.002).

Aged↗