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Biomedical subjects

G C Toner

Publications and source records attributed to G C Toner.

52 records · Page 3Linked to original sources
PubMed1994

A randomised double blind crossover study of domperidone and prochlorperazine suppositories for controlling emesis in outpatients receiving chemotherapy.

Patients receiving outpatient chemotherapy, without cisplatin, were randomised to receive four doses of either domperidone 60 mg or prochlorperazine 25 mg suppositories every 4 h, starting 30 min before the chemotherapy. They were crossed over for the next chemotherapy cycle. To enable analysis of 100 patients who had received identical chemotherapy in each course, 136 patients were randomised. Patients experienced a higher grade of nausea on domperidone (P = 0.05). Only 18% of patients vomited on domperidone and 14% on prochlorperazine, but the number of vomits was higher on domperidone (P = 0.003) and the duration was significantly increased (P = 0.02). Patients experienced significantly more diarrhoea on domperidone (P < 0.0001), although it was predominantly mild. Patients were significantly more sedated on prochlorperazine on the second course (P = 0.006), but not on the first course (P = 0.9). More patients preferred their second course (P < 0.0001), and were significantly less anxious (P = 0.0002). Patients reported tolerating their treatment similarly for both antiemetics, but more patients preferred prochlorperazine (P = 0.003), mainly due to reductions in nausea and vomiting and other side-effects, particularly diarrhoea.

Adult↗
PubMed1994

Phase I trial of intravenous and intraperitoneal administration of granulocyte-macrophage colony-stimulating factor.

To assess the toxicity, pharmacokinetics, and local and systemic effects of the intraperitoneal (i.p.) administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) at various dosages, 13 patients with predominantly i.p. malignancies refractory to standard chemotherapy were studied. GM-CSF was administered intravenously (i.v.) for 5 consecutive days; 21 days later the same dosage of GM-CSF was administered i.p. for 5 consecutive days. Four dosage levels were studied: 1, 2, 4, and 8 micrograms/kg/day. GM-CSF was well tolerated after i.v. and i.p. administration at doses up to 8 micrograms/kg/day. A transient fall followed by an elevation of circulating white cells was observed over a 24-h period after both i.v. and i.p. GM-CSF administration (mean minimum +/- SE as % baseline): 38 +/- 8% at 30 min after i.v. administration, 21 +/- 5% at 60 min after i.p. administration; mean maximum: 220 +/- 41% at 6 h after i.v. administration, 202 +/- 39% at 12 h after i.p. administration). The magnitude and time course of these changes were very similar for the two routes despite an up to 400-fold difference in serum GM-CSF levels at the same time points. Changes in leukocyte count and differential and neutrophil function were also similar over the 3-week period after both i.v. and i.p. administration. In the only patient who had i.p. GM-CSF levels assayed, i.p. administration achieved high levels of GM-CSF in peritoneal fluid (Cmax 343 ng/ml) with maintenance of high concentrations over 24 h (C24h 128 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Extragonadal and poor risk nonseminomatous germ cell tumors. Survival and prognostic features.

One hundred forty-nine patients with poor risk nonseminomatous germ cell tumors (NSGCT) treated between 1975 and 1988 were studied. Patients were considered poor risk if they had an extragonadal primary site or testicular NSGCT with low predicted probability of achieving a complete response (CR). Primary sites were the testis (99 patients), retroperitoneum (18 patients), and mediastinum (32 patients). Patients with mediastinal NSGCT had lower human chorionic gonadotropin (HCG) (P less than 0.0001) and lactate dehydrogenase (LDH) levels (P less than 0.0001), and more frequent yolk sac elements (P = 0.002). CR rates were 38% for mediastinal, 61% for retroperitoneal, and 38% for testicular primary sites. Mediastinal NSGCT patients more frequently required resection of residual malignancy to attain a CR (6 of 12). Mediastinal NSGCT had the worst event-free survival (P = 0.02). Cox regression analysis identified brain or liver metastases as the most important predictor of event-free survival in poor risk patients. Retroperitoneal NSGCT often have a poor outcome due to advanced presentation, but the likelihood of a CR to therapy can be predicted using criteria applicable to testicular primary tumors. Therefore, not all retroperitoneal NSGCT are poor risk, and retroperitoneal tumors are probably of occult testicular origin. Mediastinal NSGCT have distinct clinical and pathologic features, do not respond as well to chemotherapy, relapse more frequently, and have the worst survival. The likelihood of a CR cannot be predicted using criteria developed for primary testicular tumors, suggesting that mediastinal primary NSGCT is a distinct clinical entity.

Abdominal Neoplasms↗
PubMed1991

Patient selection for retroperitoneal lymph node dissection after chemotherapy for nonseminomatous germ cell tumors.

The indications for retroperitoneal lymph node dissection (RPLND) after chemotherapy for nonseminomatous germ cell tumor of the testis vary widely. We reviewed our experience with 122 patients who underwent RPLND within 6 months of receiving cisplatin-based chemotherapy for bulky (greater than 3 cm) retroperitoneal metastases. Pathologic findings were necrotic tissue in 57 (47%), teratoma in 48 (39%), and residual malignancy in 17 (14%). The size of the retroperitoneal mass after chemotherapy (p = 0.001) and the degree of shrinkage that occurred with chemotherapy (p = 0.0001) were both strongly correlated with the histologic findings at RPLND. The presence or absence of teratomatous elements in the pretreatment orchiectomy specimens was only weakly correlated (p = 0.06). Multivariate logistic regression found shrinkage and the size of the residual mass to be independent predictors of finding only necrotic tissue. We were unable to identify preoperatively a group of patients in which some did not have teratoma or malignancy ultimately resected. Of 39 patients who had a residual mass less than 1.5 cm, and 43 patients whose residual mass was less than 1.5 cm or whose mass had shrunk by greater than 90%, 3 had residual malignancy, and 5 had teratoma resected. Among these 8 patients, 7 had prechemotherapy masses greater than 3 cm. Even with stricter criteria, of 17 patients with no testis teratoma initially and a residual mass less than 1.5 cm which had shrunk by greater than 90%, 5 (30%) had teratoma or malignancy resected. Postchemotherapy RPLND is recommended for all patients with a prechemotherapy mass greater than or equal to 3 cm, irrespective of the radiographic findings.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Serum tumor marker half-life during chemotherapy allows early prediction of complete response and survival in nonseminomatous germ cell tumors.

The prognostic value and therapeutic utility of monitoring the decay of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) after chemotherapy for nonseminomatous germ cell tumors was assessed. Patients treated on successive front line chemotherapy protocols at Memorial Hospital between 1979 and 1988 were studied. Marker values taken within the first 90 days of treatment were reviewed for the 198 patients who had initially abnormal values and serial measurements at Memorial Hospital. Since markers frequently increased in an unpredictable fashion in the first week after chemotherapy, prechemotherapy values would be inaccurate for assessment of subsequent half-life. Therefore, the first two values measured greater than 7 days after the start of treatment were used for all calculations of half-life. Among 38 patients who had the two successive AFP measurements elevated, those who later achieved a complete response (CR) had a median AFP half-life of 6.1 days (n = 20), whereas those not achieving CR had a median AFP half-life of 13.3 days (P = 0.02). Among 37 patients with the two successive HCG values elevated, those who later achieved CR had a median HCG half-life of 4.2 days (n = 10), whereas those not achieving CR had a median HCG half-life of 18.4 days (P = 0.04). Forty-two patients who had an AFP half-life greater than 7 days or an HCG half-life greater than 3 days had significantly shorter overall survival (median, 8 months) than the other 156 patients (median not reached) (P less than 0.0001). These 42 patients also achieved CR in lower proportion (29%) than the other 156 patients (89%) (P less than 0.0001). Cox regression identified prolonged marker half-life as the most significant independent predictor of survival. Lack of appropriate decay of serum tumor markers can identify patients unlikely to achieve CR or prolonged survival and thus can be used to select patients during treatment who may benefit from an early change to more aggressive therapy.

Adolescent↗
PubMed1990

Nonseminomatous germ cell tumors: enlarging masses despite chemotherapy.

In men who otherwise seem to have responded to chemotherapy for nonseminomatous germ cell tumors (NSGCTs), enlarging masses can represent benign tissue rather than residual or recurrent malignancy. One hundred eighty-five men with negative serum tumor markers after first-line chemotherapy for NSGCT underwent surgical resection of residual masses within 6 months after completing therapy. Radiologic examinations revealed 14 patients who had 17 masses (10 retroperitoneal, five pulmonary, two mediastinal) that had enlarged despite therapy. Fourteen (82%) of the masses were teratomas (13 mature, one immature), two (12%) were necrotic tissue, and one (6%) was a mature teratoma with sarcomatous transformation. All 12 retroperitoneal and mediastinal teratomatous masses were at least partially cystic at posttherapy computed tomography. Seven of the 14 patients had a differential response to therapy: Some masses regressed while others enlarged. Enlarging masses in patients with negative serum tumor markers after chemotherapy for NSGCT frequently represent mature teratomas. Complete surgical resection of such masses usually is curative and identifies patients with residual malignancy who require further therapy.

Adolescent↗
PubMed1990

Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection.

One hundred eighty-five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors (NSGCT) treated with Memorial Hospital front-line cisplatin- or carboplatin-based combination chemotherapy protocols between 1979 and 1988. Clinical, pathologic, and radiologic features were correlated with the pathologic findings at surgery. The size of a residual retroperitoneal mass, the degree of shrinkage that occurred with chemotherapy, and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy. Multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase (LDH) and alphafetoprotein (AFP) levels as the best predictors of finding only necrotic debris. No factors could be found, however, that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum. Of 39 patients with residual retroperitoneal masses measuring less than or equal to 1.5 cm in maximal diameter, three had residual malignancy and five had teratoma resected. No factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery. If serum markers have normalized after chemotherapy for NSGCT, resection of all residual abnormalities on imaging studies of the retroperitoneum, lungs, and mediastinum is recommended. In addition, retroperitoneal lymph node dissection (RPLND) is recommended for all patients with initial bulky metastases (greater than or equal to 3 cm in diameter) in the retroperitoneum, irrespective of the findings of postchemotherapy computed tomography (CT).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

The blood-brain barrier and response of C.N.S. metastases to chemotherapy.

A case demonstrating a differential effect of chemotherapy on a pineal metastasis and parenchymal cerebral metastases is described. At presentation, extensive metastatic small cell carcinoma of the lung was present and CT scanning showed an apparently solitary metastasis in the pineal. The clinical course and serial CT scans showed significant improvement of the pineal tumor and simultaneous development of multiple intra-cerebral metastases. This case confirms that the pineal gland is excluded from the blood-brain barrier, and indicates the clinical importance of the effect of the blood-brain barrier in the responsiveness of CNS metastases to chemotherapy.

Blood-Brain Barrier↗
PubMed1989

Metastatic bone marrow involvement from supraglottic squamous cell carcinoma.

A case of an aggressive supraglottic squamous cell carcinoma, which was managed with neo-adjuvant chemotherapy and radical surgery, is described. The post-operative course was of rapid deterioration and death due to progressive metastatic disease involving bone marrow and liver. This is the first reported case of bone marrow infiltration by squamous cell carcinoma of the head and neck diagnosed ante-mortem. The incidence and pattern of metastatic disease from head and neck tumours is reviewed, and the importance of initial staging in determining the risk of distant metastatic disease is emphasised.

Bone Marrow↗
PubMed1989

Central nervous system lymphoma: primary lumbar nerve root infiltration.

Primary malignant lymphoma of the central nervous system (CNS) is rare and only infrequently involves the spinal cord, usually in association with multifocal CNS spread. We report a case of primary lymphoma infiltrating lumbar nerve roots without evidence of systemic lymphoma. There has been an excellent response to combined modality therapy, comprising radiotherapy with intrathecal and intravenous cytotoxics. The patient remains well and active 22 months after diagnosis. The literature regarding these rare tumors is reviewed.

Ganglia, Spinal↗
PubMed1989

Autoantibodies to neurons and to the cytoskeleton in small cell carcinoma with paraneoplastic sensory neuropathy.

Autoantibodies to neurons and to the cytoskeleton were demonstrated in the serum of a patient with small cell carcinoma of the lung (SCCL) and paraneoplastic sensory neuropathy. The serum reacted by immunofluorescence with the nuclei of neurons, and with cytochalasin B-sensitive "stress fibres" of cultured cells. The serum also reacted by immunofluorescence with the nuclei of some cultured cell lines. Immunoblotting experiments with brain tissue, with SCCL, HeLa and other cultured cells showed that the serum reacted with 1-4 bands of 35-39 kDa apparent m.w. Two dimensional immunoblotting showed that these molecules had a neutral pI. Antibodies, affinity-purified by elution from the 35-39 kDa bands, gave staining of the nuclei of neurons and of cultured cells and immunoblotted the same 35-39 kDa antigens. These observations show that the anti-neuronal autoantibody reacts not only with neurons and with SCCL but also with some cultured cell lines. Molecular mimicry has been invoked as the basis for the reactivity of this autoantibody with exposed epitopes on SCCL and on neurons.

Animals↗
PubMed1987

Lethal skin cancers in hairy cell leukemia (two case reports).

2 patients with hairy cell leukemia (HCL) complicated by multiple cutaneous and other malignancies are described. The second malignancies behaved in a much more aggressive fashion than would be expected in an immunocompetent population, and were lethal in both patients. The literature regarding second malignancies in immune compromised patients, and in HCL in particular, is reviewed.

Aged↗
PubMed1986

Composite lymphoma.

A case of composite lymphoma in a young female is described. The patient was found to have lymphocyte-predominant Hodgkin's disease at presentation, but subsequent staging laparotomy revealed coexistent but distinct Hodgkin's disease and diffuse large cell lymphoma in the spleen. Possible explanations for this rare occurrence are discussed, and the literature is reviewed.

Adult↗