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Biomedical subjects

M S Aapro

Publications and source records attributed to M S Aapro.

At least 19 recordsLinked to original sources
PubMed1991

Controlling emesis related to cancer therapy.

Combinations of dopamine antagonists or high-dose metoclopramide with steroids can provide complete control of chemotherapy-related nausea and vomiting in up to 60-70% of patients undergoing high-dose cisplatin-based chemotherapy. High-dose metoclopramide probably acts as a 5-HT3 receptor antagonist, but because of its dopamine-receptor antagonism it is the cause of extrapyramidal side-effects. These compounds, and the agents used in combination with them, tend to cause sedation, an undesirable effect in the outpatient setting. Specific 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) give a similar control of chemotherapy related nausea and vomiting, with minimum side-effects. These drugs can cause headaches and constipation and some have been related to transient liver enzyme abnormalities in cancer patients; however, disease and chemotherapy might also be the cause of the enzyme anomalies. Combinations of 5-HT3 receptor antagonists with steroids may provide a very high degree of protection.

Adrenal Cortex Hormones↗
PubMed1991

Antiemetic efficacy of droperidol or metoclopramide combined with dexamethasone and diphenhydramine. Randomized open parallel study.

We have performed an open parallel randomized study of the efficacy of two antiemetic drug combinations. Dexamethasone (10 mg i.v.), diphenhydramine (25 mg i.v.), and metoclopramide (3 mg/kg, 15 min i.v.) or droperidol (1.25 mg slow push) were given 30 min before and 90 min after start of chemotherapy. Thirty-six patients treated with cisplatin-based regimens (30 mg/m2 x 3 days or 60 mg/m2 day 1 only), have been observed for 48 h after their last chemotherapy. Twelve (67%, confidence interval 95%: 41-87%) experienced no vomiting while on metoclopramide and 11 (61%, confidence interval 36-83%) were protected by droperidol. Further patient accrual was stopped because of side effects in one study arm. Moderate sedation (difficulty to keep up a conversation) was observed in 48% of those on metoclopramide versus 14% of those on droperidol (p less than 0.05). We conclude that low-dose droperidol combinations can offer antiemetic protection for patients treated with moderate-dose cisplatin-based chemotherapies. In view of the potential for severe long-term neurologic problems due to metoclopramide or droperidol, these and similar drugs should be used at the lowest possible dose.

Adolescent↗
PubMed1991

5-HT3 receptor antagonists. An overview of their present status and future potential in cancer therapy-induced emesis.

The serotonin (5-hydroxytryptamine, 5-HT) antagonists, which bind at the type 3 receptor (5-HT3 receptor), have been evaluated in several preclinical models and found to be effective in alleviating cancer therapy-related emesis. The antiemetic efficacy of ondansetron (GRF-38032F, odanserin), granisetron (BRL-43694), tropisetron (ICS-205930), MDL-72222 and MDL-73147EF, batanopride (BMY-25801-01) and several others is at various stages of investigation. Ondansetron is currently marketed in several countries and the same will soon be true for granisetron. At this stage it is not yet possible to evaluate the comparative efficacy of each of these compounds, although recent preclinical data reveal some differences in the affinity of these compounds, for other receptors. Side effects related to these agents have been minor, consisting mainly of slight headaches; possible rises in liver enzymes related to some compounds need further evaluation. Future studies will need to determine the exact role of 5-HT3 antagonists, although their cost may confine their use to patients at high risk for side effects from metoclopramide.

Antineoplastic Agents↗
PubMed1987

[Clonogenic assays in the evaluation of antitumor chemotherapy].

Clonogenic cell assays are a tool for the study of tumor cells. This article reviews some promising results limited to drug evaluation. The SAKK ovarian cancer study confirms the predictive value of chemosensitivity or chemoresistance determined by these tests. Studies on the CASSG/EORTC show the reproducibility of these techniques and their usefulness in preclinical drug evaluation. Routine use of these methods is limited by inaccessibility of tumor cells and no-growth rate.

Antineoplastic Agents↗
PubMed1987

Colony formation in vitro as a prognostic indicator for primary breast cancer.

Cells from some, but not all, tumor biopsy samples form colonies when cultured in semi-solid media. The possibility that colony formation by progenitor cells in these tumors may reflect a more "aggressive" phenotype bearing clinical implications was examined in a series of 61 patients with primary breast cancer. Tumor cells from 32 samples formed colonies in vitro. There was no correlation between colony formation and any of the standard clinical parameters such as tumor size, nodal status, metastatic spread, or hormone receptor levels. Eighteen patients had inflammatory, locally advanced and/or detectable metastatic breast cancer at the time of surgery. Sixteen of these patients have progressed and 15 have died, with no relationship between colony formation and survival. For the 43 remaining patients, 23 had a tissue sample that gave rise to colonies in vitro; 14 of these have relapsed, with a median relapse-free survival (RFS) of 37.6 months, and eight have died with a median survival time of 46.8 months. This is compared with four relapses (median RFS not reached, P = .0043, Peto-Pike), and four deaths (median not reached, P = .1175) in the group without growth of the tumor specimen. These results indicate that colony formation is an independent prognostic parameter for breast cancer, which may be useful for selecting patients who would benefit from more intensive therapy.

Adult↗
PubMed1986

Sodium azide is less suitable as a positive control of drug-induced lethality for in vitro clonogenic assays.

Sodium azide (6 mg/ml) was used as a positive control for drug-induced lethality in an in vitro clonogenic assay. Petri dishes containing control and sodium azide treated cultures of WiDr cells were placed together in a large Petri dish and incubated at 37 degrees C in an atmosphere of 10% CO2 in air. No growth was observed. Control cells formed colonies only when the dishes were separated from the sodium azide dishes. Using a microtiter plate the toxic effect was inversely related to the distance of the test cultures from the sodium azide treated cultures. These results suggested the formation of a toxic gas or vapour from sodium azide under cell culture conditions, probably an azide. Chemical analysis was based on characteristic reactions, such as the production of a precipitate with silver ions or formation of a red-coloured complex with ferric salts. On a microtiter plate, a gradient of the expected precipitate or red colour was observed, the highest amounts adjacent to the wells containing sodium azide. These results show that sodium azide acts as a positive control of drug-induced lethality for in vitro clonogenic assays. However, the formation of a highly toxic vapour, most likely hydrazaic acid, makes it a less suitable standard.

Azides↗
PubMed1986

Phase I study of cyclohexylamine and lysine salt of mafosfamide.

Mafosfamide is a new oxazaphosphorine that breaks down spontaneously into 4-hydroxy-cyclophosphamide. A phase I trial with cyclohexylamine and lysine salts of mafosfamide was carried out in 16 patients, using weekly IV perfusion. Dose-limiting toxicities were not hematological, but consisted in the development of severe pain along the vein during administration. A particular mucosal syndrome with sneezing and conjunctivitis was seen only after administration of the lysine salt. The dose of 700 mg/m2 per week represents the maximum tolerated dose with this weekly schedule.

Adult↗
PubMed1986

Preliminary analysis of combined treatment with prednimustine and 4'epidoxorubicin in advanced breast cancer.

In an effort to define a well-tolerated therapeutic regimen for advanced breast cancer, we have studied a combination of 4'epidoxorubicin, 50 mg/m2 IV on day 1, and prednimustine, 100 mg/m2 PO on days 3 to 7 given every 3 weeks. Twenty-nine patients have been entered, and 22 are presently evaluable for response. Median age of the evaluable patients is 62 (range, 36 to 77), and median performance status (SAKK) is 2. Five patients had received chemotherapy, 16 hormonal therapy, five radiation therapy, and five no prior therapy for advanced disease. Most patients were in a high-risk group, with dominant visceral metastatic sites in 19 out of 22 cases. We have observed eight partial responses, nine no changes, and five progressions. Median response duration is 6 months. It is too early to discuss median overall survival. Toxicity is evaluable in 27 patients who received at least one course with a full dose of chemotherapy. Hematologic toxicity has been low, with only four patients having leukocyte nadirs below 2000/mm3 and three patients with thrombocyte nadirs below 100,000/mm3. Major alopecia (requiring a wig) was observed in eight patients. Emesis (controlled by minor antiemetics) was reported in six cases. This well-tolerated regimen is active in advanced high-risk elderly breast cancer patients, but dosage might be too low for younger patients and nonpretreated patients.

Adult↗
PubMed1986

Primary pulmonary Hodgkin's disease and the dilemma of E stage.

Primary pulmonary Hodgkin's disease is rare. We report the case of a previously healthy 23-year-old woman who presented with isolated involvement of the right upper pulmonary lobe. Nodular sclerosing Hodgkin's disease was diagnosed after curative surgery. The clinical stage is felt to be IEBL+. The reasons for this staging, as opposed to a stage IV, are discussed. Adjuvant radiotherapy was given, delivering 39.6 grays in 22 courses of 1.8 grays. Three years after diagnosis, the patient is well and free of disease. A review of the literature indicates that the majority of primary pulmonary Hodgkin's disease present as a single mass amenable to curative surgery and radiation therapy. Chemotherapy can be reserved for the rare diffuse presentation.

Adult↗
PubMed1985

Growth of solid tumor cells in clonogenic assays: a prognostic factor?

Clonogenic assays can be used to study several characteristics of hemopoietic and solid tumor cells. Treatment of ovarian cancer patients, anticancer drug development and studies of tumor cell biology (self-renewal and cytogenetics) seem to be facilitated by these techniques, in spite of their limitations. This paper reviews data showing that good in vitro clonal growth might be a poor prognostic factor. These results are remarkable but only few patients have been studied and detailed analyses looking at other prognostic factors are lacking. However, studies of in vitro growth characteristics of hemopoietic malignancies have shown similar results. Further follow-up should substantiate these initial findings in solid tumors.

Breast Neoplasms↗