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Biomedical subjects

P Y Holoye

Publications and source records attributed to P Y Holoye.

At least 19 recordsLinked to original sources
PubMed1978

Endocrine studies in testicular tumor patients with and without gynecomastia: a report of 45 cases.

Prolactin (PRL), human placental lactogen (hPL), the beta-subunit of human chorionic gonadotropin (betahCG), testosterone (T), estrone (E1), and estradiol (E2) were measured in blood samples from 45 patients with testicular tumors, 27 of whom had gynecomastia at some stage of their disease. Forty-two of the 45 patients had at least one abnormal hormone level. The most common abnormality was that of plasma estrone: it was elevated in 32 out of 42 (76%) patients in whom it was measured, suggesting a useful role for E1 as a testicular tumor marker. Prognosis was notably worse in patients with embryonal carcinoma, teratocarcinoma, and choriocarcinoma, in those with gynecomastia and, particularly, galactorrhea. Such patients also had the highest incidence of hormonal abnormalities as well as the most extreme absolute values. Hormonal mechanisms were implicated in the development of gynecomastia and galactorrhea. Prolactin, betahCG, E1, and E2 levels in all permutations correlated significantly among patients with gynecomastia, but not among those without, while estrogen to testosterone ratios were elevated in patients with galactorrhea.

Adolescent↗
PubMed1978

Chemoimmunotherapy of small cell bronchogenic carcinoma.

Thirty-one patients with small cell bronchogenic carcinoma were treated with a regimen of cyclophosphamide, Adriamycin and vincristine. Radiotherapy was given to patients with limited disease. Nonspecific immunotherapy consisting of BCG scarification was administered after each chemotherapy course. The results of treatment for this group were compared with those for a group of 45 patients treated similarly but with no immunotherapy. Therapeutic results, expressed in length of survival and rate of response, were similar. Myelosuppression was not modified by the addition of BCG scarification. This study showed no benefit from the use of such nonspecific immunotherapy.

Adult↗
PubMed1978

Combination chemotherapy of head and neck cancer.

A total of 77 patients with cancer of the head and neck area were treated with five different drug combination regimens. Five of the 77 patients had lymphoepithelioma; four had adenocystic carcinoma, and 68 had squamous-cell carcinoma of the head and neck (16 from the skin). Of these 77 patients, 16 had no previous treatment, five had surgery, 11 had radiotherapy, and 45 had surgery and radiotherapy. The first regimen consisted of a four-day Bleomycin infusion followed after a 24-hour rest, by cyclophosphamide (Cytoxan), Vincristine (Oncovin), methotrexate and 5-Fluorouracil (5-FU) (B-COMF). The next three regimens consisted of a four-day Bleomycin course, followed by either Cytoxan and methotrexate (B-CM), Cytoxan and 5-FU (B-CF) or Methotrexate and 5-FU (B-MF). The fifth regimen consisted of Bleomycin concomitant with Cytoxan, Methotrexate, and 5-FU (B-CMF). Of the 49 patients receiving B-COMF and B-CMF, 12 showed a complete response and 12 a partial response. Among the 28 patients receiving Bleomycin, followed by any one of the two drug regimens, only six showed a partial response. The severity of the thrombocytopenia, number of drugs, lymphoepithelioma histology and performance status of the patient influenced the rate of response. Drug toxicity consisted mostly in myelosuppression. The B-CMF combination is highly effective and can be used as an adjuvant to surgery and/or radiotherapy.

Adolescent↗
PubMed1978

The pharmacokinetics of bleomycin in man.

A series of studies were carried out to investigate the pharmacokinetics of the antineoplastic antibiotic bleomycin in patients with neoplastic disorders. Drug was administered by long (four to five days) and short (10 minutes) zero-order infusions, and serial plasma and urine samples were collected. Serum and urine bleomycin concentrations were determined by radioimmunoassay. The disposition of bleomycin after the 10-minute infusion was described by a two-compartment open model. However, following multiple-day infusion estimates were obtained that were inconsistent with those from the short infusion. Parameters from the long infusions agreed with those from the short infusion when terminal plasma bleomycin levels less than 10 microunits/ml were excluded. The time to reach steady state following the long infusion (ca. 12 hours) was consistent with the half-life (3 hours) predicted by the short infusion and the long infusion excluding levels less than 10 microunits/ml. Possible explanations include assay interference by an unknown metabolite or strong binding of drug to tissues with release at a rate much less than the apparent rate of elimination of drug from the body.

Adult↗
PubMed1978

Bleomycin hypersensitivity pneumonitis.

Three patients developed radiologic and functional pulmonary changes after bleomycin therapy similar to ones previously associated with administration of this drug. However, biopsy specimens showed a pattern consistent with hypersensitivity pneumonitis rather than the interstitial pneumonia usually reported in bleomycin pulmonary toxicity. There was a patchy eosinophilic infiltrate surrounding small airways and distal air spaces, but no immune deposits were noted by ultrastructure or immunofluorescence using conventional techniques and a specific antibody against bleomycin. Two of the patients had peripheral eosinophilia of 12% and 16%. All three patients showed considerable improvement on chest roentgenogram after corticosteroid treatment. Our findings are consistant with the view that bleomycin hypersensitivity pneumonitis has a different pathogenesis than bleomycin interstitial pneumonitis. Its recognition as a separate entity seems warrnated because of the favorable response to steroid therapy.

Adolescent↗
PubMed1977

Combination chemotherapy and radiation therapy for small cell carcinoma.

A three-drug combination of the chemotherapeutic agents cyclophosphamide, vincristine sulfate, and doxorubicin hydrochloride was given to 45 patients with small cell bronchogenic carcinoma. In addition, patients with limited disease received radiation therapy to the primary tumor. The complete response rate was 44%, with a median survival of 50 weeks. The partial response rate was 29%, with a median survival of 35 weeks. Patients who did not respond to therapy showed a median survival of only 12 weeks. Twenty percent of the patients had their first recurrence in the brain, and the median survival from the time of disease recurrence was ten weeks. Bone marrow metastasis was encountered in 24% of the patient population, but this did not adversely affect survival.

Brain Neoplasms↗
PubMed1977

Clinical pharmacology of bleomycin following intravenous infusion as determined by radioimmunoassay.

The clinical pharmacology of bleomycin administered by continuous intravenous infusion over a 4 to 5 day period was examined by nine patients. Patients receiving 30 units per day attained an average steady state plasma level of 145.8 (+/- 43.1) ng/ml bleomycin. Elimination of bleomycin was initially described by first order rate kinetics (t 1/2 = 1.32 +/- 0.39 hour). However, at times greater than 12 hours following termination of infusion, a second elimination phase was observed (t 1/2 = 8.9 +/- 2.7 hour). There was also a high correlation between renal bleomycin clearance and creatinine clearance. The importance of renal clearance was indicated in a patient with renal impairment. This patient attained a steady state bleomycin concentration of 1046 ng/ml and exhibited a terminal elimination half-life of 33 hours. Overall plasma clearance of bleomycin (Qbeta) was generally greater than renal clearance, indicating that a nonrenal clearance mechanism was also important in bleomycin elimination. This nonrenal mechanism became especially apparent during renal failure.

Adult↗
PubMed1976

Large-dose bleomycin therapy and pulmonary toxicity. A possible role of prior radiotherapy.

Bleomycin sulfate pulmonary toxicity was encountered in nine of 101 patients receiving high-dose therapy for widespread testicular cancer. The pulmonary presentation was separable into two categories: (1) an early or minimal from with dyspnea on exertion, minimal roentgenographic findings, and normal arterial partial pressure of oxygen at rest and (2) a severe form, with prominent roentgenographic findings and hypoxemia at rest. All five patients with the severe form died, while the remaining four patients with the minimal presentation recovered. Prior thoracic radiotherapy appeared to predispose to bleomycin pulmonary toxicity, as this complication developed in five of 12 patients receiving prior chest radiotherapy vs four of 89 not receiving radiotherapy (p less than .001). The fatality rate of 5% with high-dose bleomycin therapy is acceptable in view of the 75% response rate and substantially improved survival achieved with bleomycin combination chemotherapy in metastatic testicular cancer.

Adolescent↗
PubMed1976

Bleomycin (NSC-125066) followed by cyclophosphamide (NSC-26271), vincristine (NSC-67574), methotrexate (NSC-740), and 5-fllorouracil (NSC-19893) for non-oat cell bronchogenic carcinoma.

The in vivo observation that bleomycin may be used as a synchronizing agent provides the basis for testing 4 days of continuous bleomycin infusion followed by 5 days of intensive chemotherapy with cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil. Thirty-eight patients with extensive non-oat cell bronchogenic carcinoma (adenocarcinoma[17 patients], squamous cell carcinoma[14 patients], and poorly differentiated carcinoma [seven patients]) were registered for chemotherapy. There were 11 patients with 50% regression of all measurable lesions and four with improved but poorly measurable radiographic lesions, providing a crude response rate of 39% (15 of 38 patients). An overall survival median of 19 weeks compares favorably with Veterans' Administration Lung Cancer Study Group control data, but was not substantially better than our own historical controls (P = 0.15). The median survival for responders was 36 weeks compared to 16 weeks for historical controls (P = 0.001) and 12 weeks for nonresponders (P less than 0.001).

Adenocarcinoma↗
PubMed1975

Bleomycin combination chemotherapy in the management of testicular neoplasia.

Eighty-three patients with Stage II or Stage III germinal neoplasia of the testis and 7 patients with extragonadal primary tumors were treated with bleomycin plus vinblastine, or a five-drug program, bleomycin plus cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil. Of the 70 Stage III patients, there were 53 responses (75%), 22 complete and 31 partial. The mean survival of the complete responders is 100+ weeks, with 3 dead. The mean survival of the partial responders and nonresponders is 38 weeks and 33 weeks, respectively. There is a highly significant difference between complete responders vs. partial and nonresponders (p less than 0.01). Thirteen patients with nonmeasurable disease (Stage II and Stage III postresectional status) but at great risk to develop widespread metastasis were treated prophylactically after conventional therapy. Nine continue in complete response to 36 months. The 7 extragonadal primary patients showed 4 partial responses, none complete. Major toxicity was myelosuppression and also bleomycin pneumonitis in 5 of the 90 evaluable patients.

Abdominal Neoplasms↗
PubMed1975

Cyclophosphamide, vincristine and sequential split-course radiotherapy in the treatment of small cell lung cancer.

Thirty-nine patients with small cell lung cancer were treated with large dose intravenous cyclophosphamide combined with vincristine. Sequential split-course radiotherapy was added when the gross disease was limited to one hemithorax and draining scalene nodes. Fifteen of 16 patients in the limited disease category showed objective response, eight of which were complete. Fourteen of 23 patients in the extensive disease category yielded an objective response, six of which were complete. The median survival for complete responders was 48 weeks, 38 weeks for partial responders and 14 weeks for non-responders. The difference between responders and non-responders was statistically significant. The major toxicity was myelosuppression with a median leukocyte nadir of 500/mm-3 noted on treatment day no. 15. Prompt recovery was the rule. Toxicity appeared to be cumulative for patients receiving radiotherapy. These results are superior to those evolving from treatment with cyclophosphamide as a solitary agent.

Adult↗
PubMedDate not supplied

Combination chemotherapy with bleomycin (NSC-125066), vincristine (NSC-67574), and methotrexate (NSC-740) plus split-course radiotherapy in the treatment of non-oat-cell bronchogenic carcinoma.

Twenty-seven unselected patients with limited disease non-oat-cell bronchogenic carcinoma were treated with a chemotherapy- radiotherapy protocol which consisted of bleomycin, vincristine, and methotrexate followed by split-course radiation. There were 15 objective responders with a median survival time in excess of 70+ weeks in contrast to a median survival time of 26 weeks for nonresponders (P less than 0.01). Objective benefit was limited to the epidermoid carcinoma group since none of the adenocarcinoma group achieved a greater than 50% reduction in maximum tumor diameter. The median survival time for the entire groups was 42 weeks in contrast to a recent split-course radiotherapy historical control group whose median survival time was 38 weeks. Toxic effects were predominantly gastrointestinal.

Administration, Oral↗