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Biomedical subjects

R L Richardson

Publications and source records attributed to R L Richardson.

At least 19 recordsLinked to original sources
PubMed1992

A phase II study of recombinant human alpha-interferon in advanced hormone-refractory prostate cancer.

To determine the efficacy of recombinant human leukocyte alpha-interferon (IFL-RA) in advanced hormone-refractory prostate cancer, the authors treated 40 patients with IFL-RA administered intramuscularly at a dose of 10 x 10(6) U/m2 three times weekly. Toxicity was substantial and necessitated at least a 50% dose reduction in all but five patients during the first 1-2 months of therapy. No responses were observed in patients with bone metastases, but complete and partial regression of nodal disease were observed in two patients with extraosseous disease (overall response rate, 5%; 95% confidence interval, 0.64-17.75%). The authors conclude that IFL-RA cannot be recommended at this dose and schedule in patients with advanced prostate cancer, but additional study of its use in patients with nodal disease may be warranted.

Adenocarcinoma↗
PubMed1992

Expression of transforming growth factor-beta (TGF-beta 1) and insulin-like growth factor II (IGF-II) messenger RNA in the developing subcutaneous tissue (SQ) of the fetal pig.

Studies (in situ hybridization) were performed on the developing subcutaneous tissue (SQ) of the pig fetus to determine sites of synthesis of TGF-beta 1 and IGF-II. Tissues from 50, 70, 90, 110-day-old pig fetuses and 7-day-old postnatal pigs were Bouin's fixed, paraffin embedded and hybridized with biotin labelled cDNA probes. The expression of TGF-beta 1 messenger RNA was detectable primarily in the dermis, hair follicle fat lobule, outer and inner SQ areas at all ages. Cells adjacent to adipocyte clusters and some small adipocytes were positive for TGF-beta 1. There was no positive hybridization of TGF-beta 1 probes in the developing muscle below the SQ. The expression of IGF-II was evident in the developing muscle below the SQ at 50 d and 70 d, and could be detected in the outer and inner SQ at 70 d. Much lower levels of IGF-II expression were observed in 90 and 110 d fetuses, but an increase in IGF-II expression was evident in the muscle of 7d postnatal pigs. Our results suggest that paracrine and autocrine regulatory systems may be operative for developing adipocytes (TGF-beta 1) and muscle (IGF-II), with specific areas and times of TGF-beta 1 and IGF-II expression being evident in developing pig SQ tissue.

Animals↗
PubMed1990

Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole).

Pirozantrone hydrochloride, an anthrapyrazole analogue, was selected for clinical evaluation based on broad antitumor activity against murine tumor systems and on potentially less cardiotoxicity when compared to anthracyclines. This anthrapyrazole analogue is currently under clinical evaluation, and we now report results on a Phase I clinical trial incorporating a pharmacologically guided dose-escalation scheme. Dose escalation was designed to proceed by factors of 2 until the patient drug exposure (concentration x time) was 40% of the murine exposure at the LD10 dose (90 mg/m2). Thereafter, more moderate dose escalations were employed. The target concentration x time value (59 micrograms-min/ml) derived from preclinical pharmacology data was exceeded in all three patients at a dose of 90 mg/m2. A dose of 160 mg/m2 was found to reproducibly result in appropriate myelosuppression. This dose is recommended for further testing in Phase II studies. Nonhematological toxicities encountered in this trial were mild, the most notable being phlebitis at the infusion site. Objective responses were observed in two patients, one with metastatic breast cancer and another with metastatic melanoma. Following a 60-min infusion, pirozantrone hydrochloride plasma elimination was monoexponential, with a half-life of approximately 30 min, mean total body clearance of 1.29 liters/min/m2, and mean steady state volume of distribution of 29 liters/m2.

Adult↗
PubMed1990

Cranial nerve lesions due to base of the skull metastases in prostate carcinoma.

We studied 11 patients with prostate cancer metastatic to the base of skull that caused cranial nerve deficits. Patients with occipital condyle, jugular foramen, middle fossa, parasellar, and orbital syndromes are described. Other patients had combinations of these syndromes or other cranial nerve involvements. Two patients had 6th nerve palsies secondary to prepontine cistern and clivus lesions. The median survival time from the diagnosis of cranial nerve involvement was 4 months. Two patients had cranial nerve involvement and, on subsequent investigation, were found to have carcinoma of the prostate. Interestingly, these patients are still alive at 42 and 84 months after diagnosis.

Aged↗
PubMed1990

Synchronous and metachronous bilateral testicular tumors. Mayo Clinic experience.

The authors report a retrospective review of their experience with bilateral testicular cancers over two 10-year periods, one each from the prechemotherapy era (1935-1944) and the postchemotherapy era (1977-1986). Three of 295 patients (1.02%) evaluated at Mayo Clinic (Rochester, MN) for testicular germ cell malignancy between 1935 and 1944 had evidence of bilateral testicular malignancy. Two of these were synchronous and one metachronous occurring 3 years after the first diagnosis. In all three, the histology was pure seminoma. None of these three had a history of undescended testes. Both patients with synchronous tumours died within 2 years (6 months and 2 years, respectively) in spite of appropriate treatment at that time, and the one with metachronous tumor survived long-term (47 years). During the modern chemotherapy era, 16 of 500 (3.2%) patients evaluated at the Mayo Clinic Rochester between 1977 and 1986 for testicular germ cell malignancy had evidence of bilateral testicular cancers (four of these were synchronous and 12 metachronous [eight seminomas, four non-seminomas]) occurring between 1 to 15 years after the first diagnosis. Only two of 16 had a history of undescended testes surgically corrected while the patients were in their teens. All patients did well after appropriate treatment. This study reemphasizes the small but definite risk for development of a second testicular malignancy and suggests a recent increase in incidence of bilateral testicular tumors as possibly related to improved treatment modalities with a higher cure rate of the original tumor.

Adolescent↗
PubMed1990

Phase I and clinical pharmacological evaluation of a parenteral hexamethylmelamine formulation.

Hexamethylmelamine has been evaluated in single agent and combination regimen studies for many years, but only following p.o. administration. Pharmacological studies in animals and humans have shown that systematic availability of parent drug following p.o. administration is relatively low and variable due to extensive first-pass metabolism rather than due to poor absorption. Two Phase I clinical trials, with accompanying pharmacokinetic studies, have been conducted by using a parenteral formulation in which hexamethylmelamine was prepared by Intralipid 10%. The parenteral formulation was well tolerated by all patients receiving hexamethylmelamine by 1-day and by daily for 5-days schedules. Nausea and vomiting were the dose-limiting toxicities. Maximally tolerated doses on the 1-day and daily for 5-days schedules were approximately 850 mg/m2 and 630 mg/m2/day, respectively. No responses were observed in either study. Following i.v. administration of 540 mg/m2 hexamethylmelamine, plasma elimination was best described by a three-compartment open model with terminal half-life, total body clearance, and steady-state volume of distribution values of 10.4 h, 0.75 liter/min/m2 and 460 liters/m2, respectively. Twenty-four h urinary recoveries of parent drug were less than 1% for all patients. Accumulation of hexamethylmelamine during the 5-day treatment at 945 mg/m2 suggested possible saturation of parent drug elimination at that dose. Phase II studies are currently under way with the parenteral formulation of hexamethylmelamine.

Altretamine↗
PubMed1990

Modern radiotherapy results with bulky stages II and III seminoma.

We treated 20 patients with stage II seminoma by primary radiotherapy from 1971 to 1982. Median patient age was 38 years (range 26 to 52 years) and median disease width in the transverse plane was 11 cm. (range 5 to 25 cm.). Four tumors were 5 to 9 cm., 9 were 10 to 14 cm. and 7 were 15 cm. or more wide. Tumor was palpable in 13 patients. Generous radiation ports (such as wide hockey stick or whole abdomen) often followed by a boost to the area of bulky disease were used as primary therapy in all patients. Median tumor dose was 37.5 Gy. (range 13.3 to 56.7 Gy.). Supradiaphragmatic prophylactic radiation was given to 16 patients (median dose 26 Gy., range 12 to 37.3 Gy.). Median followup was 56 months, and all patients currently are free of disease except for 1 who died without disease more than 10 years after completion of all therapy. Mediastinal failure occurred in 2 of 4 patients without and 1 of 16 with mediastinal prophylaxis. All 4 patients with relapse are currently free of disease after salvage therapy. Five patients 16 to 42 years old (median age 30 years) received primary radiation therapy for stage III disease. The median size of abdominal disease was 10 cm. (range 5 to 17 cm.). Of the 5 stage III cancer patients 3 had supradiaphragmatic disease demonstrated only in supraclavicular lymph nodes and all 3 were continuously free of disease 115 to 136 months after therapy. The remaining 2 stage III cancer patients had supradiaphragmatic disease by virtue of bulky mediastinal disease with or without supraclavicular involvement. Both patients had relapse in-field and distantly, and they died of disease despite salvage chemotherapy. A total of 30 fields with bulky disease (greater than 5 cm.) was treated either primarily or at relapse among the 25 stages II and III cancer patients. In-field relapse occurred in 3 of 21 patients receiving less than or equal to 36 Gy. and 0 of 9 who received greater than 36 Gy. These results justify radiation therapy as an acceptable initial primary treatment modality for typical bulky stage II seminoma. Disease greater than 5 cm. should receive greater than 36 Gy. Prophylactic radiation to the mediastinum is effective. However, patients who have mediastinal failure often can be salvaged with chemotherapy and/or radiation, and prophylactic mediastinal radiotherapy may be associated with poor tolerance to salvage chemotherapy and other significant late effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Familial testicular cancer: report of six cases and review of the literature.

The cause of testicular cancer, like most other cancers, is unknown. Certain risk factors such as cryptorchidism, carcinoma in situ, and a preceding contralateral testicular germ cell neoplasm are known to predispose a person to the subsequent development of a testicular malignant lesion. Familial testicular cancer has been debated as a potential and possibly independent risk factor. Evidence in favor of such a hypothesis, based on various genetic studies reported during the past few decades, is reviewed. We add to the existing literature our experience with six cases of familial testicular cancer encountered during a 10-year period, consisting of four father-and-son pairs, one pair of nontwin brothers, and a 23-year-old man who had a maternal uncle with a history of testicular cancer.

Adult↗
PubMed1990

Observation after orchiectomy in clinical stage I nonseminomatous germ cell tumor of testis. Mayo Clinic experience.

We report a retrospective review of our experience with close observation after orchiectomy in clinical stage I nonseminomatous germ cell tumors (NSGCT) of the testis during a 10-year period. Twenty-four patients were followed between 1977 and 1986 for a median duration of 47 months (24-112 months). Six of 24 (25%) relapsed at a median of 3.5 months (2-46 months) after orchiectomy; all of these were treated with chemotherapy and are in complete remission at a median of 55 months (27-69 months) after diagnosis of recurrence. Eighteen other (75%) who did not relapse are without evidence of disease at a median of 39 months (24-112 months) after orchiectomy. Orchiectomy alone followed by close observation in clinical stage I NSGCT is a reasonable approach in reliable patient populations at well-equipped centers where adequate follow-up is possible.

Adolescent↗
PubMed1990

Life-threatening bleomycin pulmonary toxicity with ultimate reversibility.

A 60-year-old man with advanced seminoma was treated with four cycles of a cisplatin, etoposide and bleomycin. He then developed severe pulmonary toxicity with diffuse infiltrates as evidenced on a chest x-ray film. The room air PaO2 value was 32 mm Hg. The patient was treated with steroids and oxygen supplementation, including a high FIo2 for several days, and survived and eventually experienced marked improvement in his pulmonary status. Aggressive management of severe bleomycin-induced pneumonitis appears justified.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung.

From October 1979 to December 1982, 126 patients with locally advanced unresectable or inoperable Stage II (7 patients), Stage IIIA (81 patients), and Stage IIIB (38 patients) non-small cell carcinoma of the lung were treated in a prospective randomized trial using five cycles of CAP (Cytoxan, Adriamycin, and cisplatin), T-CAP (triazinate plus CAP), or V-CAP (VP-16 plus CAP) chemotherapy with thoracic radiation therapy (TRT). TRT consisted of 40 Gy in 10 fractions (split-course) with cycles 3 and 4 of chemotherapy. The treatment field included the primary tumor, ipsilateral hilum, mediastinum, and ipsilateral supraclavicular fossa. All patients were followed until death or for a minimum of 5 years for survivors. The evaluable subgroup consisted of 102 patients who completed TRT. Median and 5-year survivals for the entire group were 14.0 months and 10%, respectively; for the evaluable subgroup, they were 14.8 months and 12%, respectively. There was a trend toward better survival with V-CAP plus TRT than with CAP plus TRT (p = 0.08). Median and 5-year survivals were 16.2 months and 18%, respectively, with V-CAP plus TRT. Of eight prognostic variables analyzed for their association with survival, only Eastern Cooperative Oncology Group performance status (0,1 versus 2) (p = 0.02) and weight loss (less than or equal to 10% versus greater than 10%) (p = 0.05) were significant. Sex, age, T stage, N stage, overall stage, and histologic type were not significantly associated with survival. Failure analysis revealed 83 patients (81%) with identifiable first failures. The median time to first failure was 9.8 months, and the median survival after first failure was 4.7 months. Failure patterns included local failure alone (19%), local and distant (20%), and distant alone (43%). Nineteen percent of patients had no documented progression. Total failure patterns were local in 39% and distant in 63%. Twenty-three patients (23%) had failure in the brain; they accounted for 31% of all distant failures. In 20 of these patients (20% of all patients), this was the only site of failure. There were eight (8%) initial nodal failures in 96 untreated contralateral supraclavicular fossae. No initial failures were seen in any of 101 untreated contralateral hila. The data suggest the following: (a) Combined treatment with V-CAP and TRT yielded excellent results (median survival, 16.2 months; 5-year survival, 18%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation.

The cases of 283 small cell lung cancer patients who received treatment with combination chemotherapy with or without prophylactic cranial irradiation (PCI) were reviewed to determine the incidence of leukoencephalopathy. The overall incidence was 10%. Of all patients receiving PCI, 17% developed neurotoxicity, and of those receiving PCI and surviving greater than or equal to 1.5 years, 37% suffered neurologic sequelae. In those receiving PCI but surviving less than 1.5 years, the incidence of neurotoxicity was 4%. The mean time interval between the end of PCI and the onset of neurotoxicity was 17 months (range 2-63 months). The PCI dose ranged from 2600-3600 cGy. None of the patients not receiving PCI developed neurotoxicity. The incidence of neurotoxicity in long-term survivors (greater than or equal to 1.5 years) with respect to PCI dose was less than or equal to 3000 cGy (25%), 3200 cGy (56%), 3600 cGy (36%). Almost all of the patients getting PCI also received lomustine, an agent associated with DNA repair inhibition and synergism with DNA damaging agents such as ionizing radiation or alkylating agents. Under the conditions of our study, PCI was associated with an unacceptable risk of neurotoxicity. Until further information is forthcoming, one should proceed with caution when using PCI in conjunction with lomustine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Transforming growth factor type beta (TGF-beta) and adipogenesis in pigs.

The present study was performed on s.c. adipose tissue of fetal pigs at 35 to 110 d of gestation to examine the distribution of TGF-beta-positive cells, to localize TGF-beta immunoreactivity at the cellular level using electron microscopy (EM), and to determine the effect of TGF-beta on primary cultures of pig adipose tissue cells. Tissues for EM were fixed and embedded in LR white resin. Sections then were incubated with a polyclonal antibody specific for TGF-beta and TGF-beta was located using 20 nm colloidal gold conjugated second antibody. Tissues were fixed and embedded in paraffin for localization of TGF-beta at the light microscope (LM) level. Tissues were incubated with anti-TGF-beta followed by localization using biotinylated second antibody. Using LM, only a few cells stained positively for TGF-beta within developing blood vessels at 35 d. By 50 d, more TGF-beta-positive cells were associated with forming capillary networks. Between 70 d and 110 d, positively stained adipocytes usually were clustered around blood vessels. Cells surrounding hair follicles stained positive for TGF-beta between 90 to 110 d. Electron microscopy revealed TGF-beta labeling within fat cells. Fibroblasts and endothelial cells did not exhibit TGF-beta immunoreactivity. The addition of TGF-beta to primary cultures of s.c. adipose tissue cells from newborn pigs prevented lipid filling in fat cells. This effect was dose-dependent, with half-maximal inhibition occurring at 3 pM maximum inhibition occurred at 40 pM. These results indicate that TGF-beta may regulate angiogenic activity and lipid filling in s.c. adipose tissue of fetal pigs. Although TGF-beta was present in adipocytes and in cells associated with developing capillary networks, the physiological role of TGF-beta during early adipose tissue development is not known.

Adipose Tissue↗
PubMed1988

A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer.

One hundred eight eligible patients with advanced, metastatic non-small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, and cisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non-cross resistance.

Aged↗
PubMed1988

Pilot study of a continuous five-day intravenous infusion of etoposide concomitant with cisplatin in selected patients with advanced cancer.

In view of experimental and clinical data suggesting enhanced antiproliferative efficacy from a continuous infusion of etoposide (VP-16) concomitant with cisplatin (CDDP), we performed a dose-seeking study of a five-day infusion of VP-16, 30 mg/m2/24 h and CDDP, 18.5 to 25 mg/m2/24 h. Among eight patients with advanced solid tumors, dose-limiting toxicities were leukopenia and thrombocytopenia. There were no clinically significant renal, neurologic, or otologic sequelae. Nausea and vomiting were mild and transient. Although the trial was not designed as a phase II assessment, we observed three objective regressions among three patients with advanced gastric adenocarcinoma who had failed prior chemotherapy. The total CDDP dose is similar to five-day single agent studies, yet the total VP-16 dose is approximately 24% to 50% less than a five-day single agent VP-16 dose. The recommended regimen for continuous 120-hour infusion is VP-16, 30 mg/m2/24 h and CDDP, 20 mg/m2/24 h, repeated at monthly intervals.

Adenocarcinoma↗
PubMed1988

Treatment toxicities in long-term survivors of limited small cell lung cancer.

A total of 211 patients with limited small cell lung cancer were assessed retrospectively for long-term toxicities, treatment-related deaths, and second primaries. All had received treatment with various combinations of doxorubicin, vincristine, cisplatin, lomustine, cyclophosphamide, and etoposide with or without split-course thoracic radiotherapy (4,000 cGy/10 fractions) and/or split-course prophylactic cranial irradiation (3,600 cGy/10 fractions). Sixty-eight (32%) of the patients survived longer than 1.5 years and formed the basis of this study. Debilitating pulmonary, cardiac, and neurologic toxicity was noted in 12%, 14%, and 15%, respectively, of long-term survivors. These complications were the result of aggressive combined modality therapy. Certain drugs appeared to cause additive toxicity when combined with radiation. Three patients developed new primary tumors of squamous cell origin. Attention must be directed to defining the safest way to employ aggressive combined modality treatment for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Small cell lung cancer. Complete remission and improved survival.

Thirty-two patients with limited-stage small cell lung cancer were treated with combined supervoltage radiotherapy and a combination of cyclophosphamide, doxorubicin and vincristine chemotherapy. The goal of obtaining a complete remission, the necessary step which precedes improved survival, was successful in 26 of 27 of completely re-evaluated patients. Fiberoptic bronchoscopy was useful in substantiating complete remission status. Seventeen of the 32 patients remain alive from 8+ to 28+ months (median 16+ months). Ten patients are alive and relapse-free from 12+ to 28+ months (median 19+ months). Transient granulocytopenia (mean nadir 650 cells/mm3) during induction therapy and the associated risk of infection were the most serious toxicities encountered. This therapy produces complete remission on roentgenography and bronchoscopy, symtomatic improvement and improved survival in the majority of patients with limited-stage small cell lung cancer. A portion of these patients may have their disease eradicated.

Adult↗