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Biomedical subjects

M S Aapro

Publications and source records attributed to M S Aapro.

At least 55 records · Page 3Linked to original sources
PubMed1996

Phase II data on paclitaxel and docetaxel in gastrointestinal malignancies.

From the contributions in this volume, it is apparent that in spite of promising chemotherapy combinations and new multidisciplinary approaches, the treatment of advanced gastrointestinal malignancies remains a difficult task. New agents have recently been developed with either a better therapeutic ratio (fluoropyrimidine analogs or modulators of the metabolic pathway of those agents) or a better activity due to a different mechanism of action. Among the latter agents, the topoisomerase I inhibitors (especially irinotecan, also known as CPT-11) and new antimetabolities (difluorodeoxycytidine, also known as gemcitabine) are of interest for difficult tumors, such as colon and pancreatic cancer. This short review describes the phase II studies on the activity of taxoids, agents that promote tubulin assembly in microtubules and inhibit their depolymerization.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature.

Recurrent and metastatic cervical carcinoma has very poor prognosis, mainly because there is no effective systemic therapy which would increase the duration of survival. Biologic agents have recently been found to have activity in cervical carcinoma. The combination of interferon (IFN)-alpha and 13-cis-retinoic acid had additive and synergistic antitumor activity. Both have antiviral, immunoregulatory and antiangiogenic properties, and are known to modulate malignant cell differentiation and proliferation. We report two patients with recurrent squamous cell carcinoma (SCC) of the cervix who had small-volume progressive metastatic disease, and were treated with a combination of IFN-alpha and 13-cis-retinoic acid. The first patient had pelvic lymph node metastases and the other had lung metastases. The previously progressive diseases remained stable for a prolonged period of time, 3 and 4 years, with a good quality of life. These cases suggest the possibility of using IFN-alpha and 13-cis-retinoic acid as a treatment for small-volume residual disease or as postinduction therapy in patients at high risk for disease recurrence.

Adult↗
PubMed1995

Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus.

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.

Adult↗
PubMed1994

Costs and benefits of antiemetic therapy.

Allocating part of the diminishing resources of the health-care system to new therapeutic approaches needs a decision analysis which should be understood by all partners. This paper defines some of the economic evaluation methods used recently. Through examples of cost/effectiveness and cost/benefit studies performed in the U.K. and Switzerland it shows that, in the European environment at least, specially now that prices are decreasing, serotonin-receptor (5-HT3) antagonists can and should be used to prevent acute nausea and vomiting.

Antiemetics↗
PubMed1994

The incidence of anticipatory nausea and vomiting after repeat cycle chemotherapy: the effect of granisetron.

Anticipatory nausea and vomiting (ANV) after repeated cycles of cytotoxic chemotherapy is thought to be a conditioned response to a conditioning stimulus. Good control of acute and delayed emesis may result in a lower incidence of ANV. We have analysed data from 574 chemotherapy patients who received granisetron as their antiemetic treatment during repeat cycle chemotherapy. Per treatment cycle, less than 10% of patients displayed symptoms of anticipatory nausea and 2% or less had symptoms of anticipatory vomiting. It is concluded that the use of granisetron as an antiemetic during the acute phase of chemotherapy may result in a lower incidence of ANV in patients undergoing repeat cycle chemotherapy.

Female↗
PubMed1994

Ondansetron plus dexamethasone is superior to ondansetron alone in the prevention of emesis in chemotherapy-naive and previously treated patients. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: This prospective, randomized, double-blind study assessed whether the addition of dexamethasone to ondansetron leads to improved control of chemotherapy--induced emesis, both in patients undergoing their first course of highly emetogenic chemotherapy and in chemotherapy-pretreated patients refractory to standard anti-emetics. PATIENTS AND METHODS: Patients were randomized to receive either 20 mg dexamethasone as an intravenous infusion or placebo plus ondansetron 8 mg 15 minutes prior to and 4 and 8 hours after the administration of chemotherapy. According to the randomisation code patients received from day 2 to day 5 either ondansetron 8 mg p.o. + placebo p.o., three times daily, or ondansetron 8 mg p.o. + dexamethasone 4 mg p.o., three times daily. Patients undergoing multiple-day treatment received intravenous study treatment on the days of chemotherapy and thereafter oral treatment as outlined above. RESULTS: A total of 215 patients were entered into the study. Of these, 207 were evaluable (111 previously-untreated and 96 previously-treated patients). In the chemotherapy-naive patients the combination of ondansetron plus dexamethasone was significantly superior to ondansetron plus placebo in protecting the patients completely from emesis (retching and vomiting) (81% versus 64%, p = 0.04). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated patients than in those receiving ondansetron plus placebo (0.8 versus 2.1, p = 0.03). In this group of patients there was significantly superior protection from emesis on the second day (p-value = 0.04), and a trend towards a better protection on the third and fourth days. On each day the active combination offered better protection from nausea with an approximately 20% difference in favor of ondansetron plus dexamethasone. In the group of established vomiters the combination of ondansetron plus dexamethansone was superior to ondansetron plus placebo in protecting the patients from acute emesis, with 70% versus 48% of the patients being completely protected (p = 0.03). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated-patients than in those receiving ondansetron plus placebo (0.9 versus 2.1, p = 0.02). In the ondansetron-plus-dexamethasone arm 55% of the patients had complete protection from nausea, retching and vomiting compared to 35% in the ondansetron-plus-placebo-treated group (p = 0.05). Overall 22% of the patients (20% in the ondansetron-plus-placebo and 25% in the ondansetron-plus-dexamethasone arm) experienced at least one, usually mild, adverse event. More patients in the ondansetron-plus-dexamethasone arm complained of epigastric pain or burning (8/101 versus 4/112, p-value = 0.16). The difference in patients reporting constipation (6/101 versus 0/112) was highly significant at a p-value of 0.008. CONCLUSIONS: The combination of dexamethasone plus ondansetron is more effective in protecting chemotherapy-naive patients undergoing their first course of highly emetogenic chemotherapy with cisplatin and chemotherapy-pretreated patients refractory to standard antiemetics from chemotherapy-induced nausea and vomiting compared to ondansetron plus placebo.

Adolescent↗
PubMed1993

Primary diffuse leptomeningeal gliomatosis (PDLG): a neoplastic cause of chronic meningitis.

Cancerous 'chronic meningitis' may be related to subarachnoid space involvement by solid tumors, hematologic malignancies or rarely intraparenchymatous gliomas. Primary leptomeningeal gliomatosis is a rare condition that is attributed to malignant transformation of heterotopic neuroglial tissue. We discuss the clinical and biological features of a patient who died with the diffuse form of primary leptomeningeal gliomatosis (PDLG). A literature search shows that a one to two months long non-specific prodromal phase followed by a fluctuating neurologic downhill course is suggestive of this disease. Cerebro-spinal fluid (CSF) cytology has been diagnostic in only 1 of 8 reported cases. Recent technical progress, including the use of GFAP (glial fibrillary acidic protein) directed antibody, may enhance the sensitivity of CSF cytologies. Diagnosis may require repeated cerebral biopsies, because the hemispheric lesions are often separated by normal tissue. PDLG must be added to the large differential diagnosis of 'chronic meningitis'.

Chronic Disease↗
PubMed1993

Preclinical activity of taxotere (RP 56976, NSC 628503) against freshly explanted clonogenic human tumour cells: comparison with taxol and conventional antineoplastic agents.

Taxotere (TER) and taxol (TA) are new antitumour agents currently undergoing clinical evaluation. We studied the antineoplastic effects of these agents (final concentrations: 4.0, 0.4, 0.04 mumol/l) on the in vitro proliferation of clonogenic cells from freshly explanted human tumours using a capillary soft agar cloning system. We also compared the activity of these new compounds to conventional antineoplastic agents (bleomycin, cisplatin, dacarbazine, doxorubicin, etoposide, 5-fluorouracil, vinblastine, interferon-alpha 2). Using a 21-28-day continuous drug exposure, 54/81 specimens (67%) were evaluable for comparisons, and using a 1-h drug exposure followed by 21-28 days incubation, 50/80 specimens (63%) were similarly evaluable. With both schedules, TA and TER showed concentration-related antitumour activity. At 0.4 mumol/l, median colony survival was 0.61 x control (range 0.09-0.96) for TA and 0.51 x control (0.15-0.81) for TER in the 1-h incubation (P = 0.0002). Median colony formation was also reduced significantly more by TER as compared to TA in the long-term incubation schedule. Statistical analysis indicated that TER but not TA was significantly more active than cisplatin (P = 0.02), doxorubicin (P = 0.01), 5-fluorouracil (P = 0.01) and interferon-alpha 2 (P = 0.01). We conclude that TER and TA are more active against in vitro tumour colony formation from freshly explanted human tumours. TER appears to be slightly more active than taxol and promises to be active against tumours resistant to conventional antineoplastics.

Antineoplastic Agents↗
PubMed1993

Advances in systemic treatment of malignant melanoma.

This paper reviews recent developments in the systemic treatment of advanced malignant melanoma. In the introduction emphasis is given to prevention and early detection of this disease. Metastatic malignant melanoma patients have a median survival of less than 1 year in the most favourable situation. Adjuvant chemotherapeutic treatment after initial surgery has not had an impact on prognosis, while immunological manipulations with interferon alfa or other agents may prove beneficial after primary surgery. In advanced disease which cannot be palliated by surgery, many approaches are under investigation. Modulation of the patient's immune response can be achieved with vaccines, monoclonal antibodies, interleukin-2 and interferons, as single agents or in combination between themselves or with peripheral blood mononuclear cells or with tumour infiltrating lymphocytes or even with chemotherapy. Immunological approaches yield a 20-30% response rate, with some possibly long-term responses. Chemotherapeutic agents have a 10-30% response rate, which is usually of short duration. Combinations of chemotherapeutic agents can increase the response rate to 50%, but an impact on ultimate survival seems unlikely. Randomised studies have shown that modulation of chemotherapy with interferon or tamoxifen improves response rates. Clinicians should be encouraged to enter their patients with malignant melanoma in therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗