Pharmacoeconomic management of patient with severe asthma in the Emergency Department: retrospective multicentric and cost of illness study.

OBJECTIVE: The aim of the study was to develop a cost-of-illness model that would investigate the costs associated with the management of patients suffering from asthma and severe asthma in the context of acute episodes managed in the emergency room. PATIENTS AND METHODS: A total of 795 records were collected between adults and paediatric patients. The data collection form reported an identification code for each patient included, gender, age, main discharge diagnosis, medical examinations carried out in the emergency room, the hospitalizations, and, if required by the patient condition, an outpatient visit performed by a pneumologist after the acute event that led the patient to the emergency room. In addition, the data collection form included information related to the pharmacological therapy taken by the patient. RESULTS: Among adult patients who had an admission with an asthma diagnosis, the average cost for the management of an adult patient in a green code in the emergency room is €330.39. As for the yellow code and the red code, the cost rises respectively to €444.04 and €808.25. The paediatric population has a slightly higher cost. As for the green code, the average cost stands at €355.87, for the yellow code €562.34 and €1,041.96 for the red code. CONCLUSIONS: Asthma and severe asthma impose a high burden on patients and society due to its chronicity, losses of productivity, and an increase in use of healthcare resources. We carried out the present observational retrospective analysis on asthma and severe asthma patients with the aim of assessing the economic impact from the Italian NHS perspective focusing also on the prescribed pharmacological therapies in the target conditions.

Effect of novel nociceptin/orphanin FQ-NOP receptor ligands on ethanol drinking in alcohol-preferring msP rats.

Activation of the NOP receptor by the endogenous ligand nociceptin/orphanin FQ (N/OFQ) reduces alcohol consumption in genetically selected alcohol-preferring Marchigian Sardinian (msP) rats. The present study evaluated the effect of three newly synthesized peptidergic and one brain-penetrating heterocyclic NOP receptor agonists on alcohol drinking in the two bottle choice paradigm. MsP rats were intracerebroventricularly (ICV) injected with the NOP receptor agonists OS-462 (0.5 and 1.0 microg), UFP-102 (0.25 and 1.0 microg) or UFP-112 (0.01 and 0.05 microg), or with Ro 64-6198 (0.3 and 1.0 mg/kg) given intraperitoneally (i.p.) and tested for 10% alcohol consumption. Results showed decreased alcohol consumption after treatment with all three peptidergic NOP receptor agonists (OS-462, UFP-102 and UFP-112). OS-462 (at the 1.0 microg dose) and UFP-102 (at the 0.25 microg dose) induced a significant increase in food intake as well. Surprisingly, Ro 64-6198 was ineffective at the 0.3 mg/kg dose, whereas it increased ethanol and food consumption at the 1.0 mg/kg dose. Pre-treatment with the selective mu-receptor antagonist naloxone (0.5 mg/kg, i.p.) reduced these effects of 1.0 mg/kg of Ro 64-6198. These findings confirm that activation of brain NOP receptors reduces alcohol drinking in msP rats and demonstrate that OS-462, UFP-102 and UFP-112 act as potent NOP receptor agonists. On the other hand, Ro 64-6198 increased alcohol drinking, an effect probably induced by a residual agonist activity of this compound at mu-opioid receptors. Overall, the results indicate that OS-462, UFP-102 and UFP-112 may represent valuable pharmacological tools to investigate the functional role of the brain N/OFQ system.

Pregnancy in immigrant women.

OBJECTIVE: We wanted to study how foreign women face pregnancy and childbirth in a society quite different from their own. METHODS: In 2004 we studied 328 pregnant women at the Department of Gynaecology at the "General Hospital Umberto I" in Rome. Information on patients' personal lives and experiences was collected. RESULTS: Women were classified into six (6) groups based on nationality, race, religion and culture. CONCLUSIONS: Arabian women had the most natural childbirths. African women had a longer duration of gestation. Women from Eastern Europe underwent frequent tests and examinations, but had the highest chance of having preterm births. Chinese women did not usually undergo many examinations and were able to tolerate pain during childbirth quite well.

Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress.

Alcoholism is a chronic relapsing disorder with substantial heritability. Uncovering gene-environment interactions underlying this disease process can aid identification of novel treatment targets. Here, we found a lowered threshold for stress-induced reinstatement of alcohol seeking in Marchigian-Sardinian Preferring (msP) rats genetically selected for high alcohol preference. In situ hybridization for a panel of 20 stress-related genes in 16 brain regions was used to screen for differential gene expression that may underlie this behavioral phenotype. An innate up-regulation of the Crhr1 transcript, encoding the corticotropin-releasing hormone receptor 1 (CRH-R1), was found in several limbic brain areas of msP rats genetically selected for high alcohol preference, was associated with genetic polymorphism of the Crhr1 promoter, and was accompanied by increased CRH-R1 density. A selective CRH-R1 antagonist (antalarmin, 10-20 mg/kg) was devoid of effects on operant alcohol self-administration in unselected Wistar rats but significantly suppressed this behavior in the msP line. Stress-induced reinstatement of alcohol seeking was not significantly affected by antalarmin in Wistar rats but was fully blocked in msP animals. These data demonstrate that Crhr1 genotype and expression interact with environmental stress to reinstate alcohol-seeking behavior.

Aspirin modulates LPS-induced nitric oxide release in rat glial cells.

Nitric oxide and prostaglandins are among the numerous substances released by activated glial cells. The aim of this study was to evaluate the effect of high-level aspirin on iNOS expression in cultured rat glial cells treated with lipopolysaccharide (LPS) as pathological stimulator. Using Western Blotting, we verified that aspirin enhanced LPS-induced iNOS expression and the presence of 15-deoxy-Delta(12,14)-prostaglandin (15d-PGJ2) suppressed this aspirin effect. However, the exposure of LPS-treated glial cells to aspirin resulted in a decrease of NO production. These results suggest that aspirin interferes with the cross-talk of prostaglandins and NO, blocking the endogenous negative control exerted by COX products on iNOS expression. On the other side, aspirin seems to act directly on iNOS reducing its activity, even if it does not completely block NO release by LPS-stimulated glial cells. Then aspirin could maintain homeostatic functions of NO, while it prevents toxic effects, corresponding to high NO concentrations.

Water and sodium imbalance in COPD patients.

Water retention and hyponatraemia are typically observed in the final stages of Chronic Obstructive Pulmonary Disease (COPD) and the onset of edema is a poor prognostic factor. For several years the pathogenesis of edema in COPD patients was attributed to heart impairment because of pulmonary hypertension, but the evidence that cardiac output is often adequate for the metabolic demands has suggested, since 1960, that the pathogenesis of edema in these patients would be correlated with gas exchange impairment and in particular with carbon dioxide (CO2) retention. The gas exchange impairment induces, in these patients several hormonal abnormalities: renin (Rn), angiotensin II (AnII), aldosterone (Ald), atrial natriuretic peptide (ANP), vasopressin (ADH) and endothelial factors are some of the factors involved. The systemic response to hypercapnia has the effect of reducing the renal blood flow and, as a result, increasing water and sodium retention with the final effect of edema and hyponatraemia. The aim of this brief review is to highlight the current knowledge on renal/hormonal abnormalities in COPD and their therapeutic implications.

Efficacy of anthracyclines and paclitaxel as first line chemotherapy in patients with visceral metastases of breast cancer.

BACKGROUND: Anthracyclines combined with paclitaxel are one of the most active schedules in patients with advanced breast cancer: response rates range from 40 to 80%, considering all metastatic sites (visceral and soft tissues). We performed a non-randomized phase II trial with anthracyclines/paclitaxel combination to evaluate response and toxicity only in patients with visceral metastases. METHODS: Twenty-seven patients (median age 50 years; range 30-72) with visceral metastases of breast cancer were enrolled in this study. Overall, 11 patients had lung metastases (41%), 10 liver (37%), 4 liver-lung metastases (15%) and 2 peritoneal carcinosis (7%). 7 patients had received adjuvant anthracycline-based chemotherapy (26%) and 10 patients adjuvant CMF combination chemotherapy (37%); 10 patients (37%) received hormonal therapy for advanced disease. Treatment schedules were: group A) 17 patients, Adriamicyn 50 mg/m2 on day 1 i.v. bolus and Paclitaxel 175 mg/m2 on day 2 i.v. 3 hours infusion, every 3 weeks; group B) 10 patients, epirubicin 90 mg/m2 on day 1 i.v. bolus and paclitaxel 200 mg/m2 on day 2 i.v., 3 hours infusion, every 3 weeks. The number of cycles administered was 141 with a median of 5 (range 3-9). RESULTS: All patients were evaluable for response and toxicity. The objective response rate was 59% - 16 patients - (15% complete and 44% partial remission), 95% C.I. 40.7-77%; 10/17 in group A and 7/10 in group B. Stable disease 30% (8 patients) and progressive disease 11% (3 patients). The median duration of response was 5 months (range 1-16); median time to progression 13 months (range 3-18) and median survival 17 months (range 4-24). The main toxicity was neutropenia, occurred in 16 patients (59%; grade IV in 7 patients, of whom 2 febrile neutropenia, and grade III in 9 patients); grade III gastrointestinal toxicity in 2 patients; grade III neurological toxicity in 1 patient; grade III stomatitis in 2 patients. No congestive hearth failure or treatment death related was observed. CONCLUSIONS: These schedules of anthracyclines and paclitaxel confirmed their efficacy in metastatic breast cancer even in patients with visceral disease. Neutropenia was the main toxicity; grade IV neutropenia was more frequently observed in epirubicin/paclitaxel arm.

A new cisplatin/gemcitabine schedule in locally advanced (IIIB) and metastatic (IV) non-small cell lung cancer: relationship between dose-intensity and efficacy. A phase II study.

BACKGROUND: Cisplatin/gemcitabine are one of the "standard" chemotherapy schedules in locally advanced and metastatic NSCLC cancer. A number of trials documented that omission of gemcitabine on day 15 and reduction of cisplatin up to 70 mg/mq are equivalent in term of response rates to "classic" administrations on days 1, 8 and 15 with cisplatin 100 mg/mq. The aim of this study was to confirm this evidence and to demonstrate that a further reduction of gemcitabine dose-intensity may be performed with the same efficacy on response. PATIENTS AND METHODS: Fifty untreated patients with locally advanced and metastatic NSCLC entered the study: 24 stage IIIB and 26 stage IV. The median age was 65 years (range 32-76); 44 males and 6 females Genicitabine was administered 1000 mg/mq weekly on days 1 and 8 followed by a 2-week rest and cisplatin 80 mg/mq on day 2 of each 28-day-cycle. RESULTS: Forty-five patients were evaluable for response and all for toxicity. The overall response rates were 35.5% with 16 partial responses (95% Confidence Interval: 32%-61%). Most of the objective responses were seen in IIIB patients (56% of the stage IIIB and 44% of the stage IV patients responded). According to the intent-to-treat-principle, the response rates were 32% (16 out of 50 patients). The median dose-intensity of gemcitabine and cisplatin was respectively 477.6 mg/mq/week (481.4 for responders) and 19.5 mg/mq/week (19.9 mg/mq for responders). The median response duration was 5 months (range 1-18) and the median time to progression was 5 months (1-21); median survival was 9 months (range 2-31). The main toxicity was haematological: thrombocytopenia grade IV in 5 patients (10%) and grade III in 11 patients (22%); neutropenia grade III-IV in 4 patients (8%); grade III anemia in 3 (6%). Asthenia was the most significant non-haematological toxicity and was observed in 19 patients (38%). CONCLUSION: This trial confirmed the efficacy of a schedule with 2 administrations of gemcitabine (on days 1, 8) and a cisplatin dose on day 2 lower than 100 mg/mq. Moreover, the same efficacy was obtained with a median-dose intensity of cisplatin and gemcitabine lower than planned in a 21-day-schedule. For safety and low toxicity, we think that this schedule provides another chance to treat patients with non-small cell lung cancer, especially the elderly or patients with coexistent medical illnesses.

Tumor markers in the diagnosis of malignant serous effusions.

To assess the possibility of increasing the detection rates of cytological examination in malignant effusions by the selection of specific tumor markers for a given type of tumor, we measured CEA, CA 19.9, CA 15.3, MCA, PSA, and AFP in malignant effusions from 89 patients with the following primary malignancies: colon, stomach, breast, liver, prostate, lung, and kidney. Cytological examination was positive in only 35 of 89 patients (40%), while the tumor markers were positive in 72 of 89 cases (80%). However, apart from small cell lung and kidney cancers, where the lack of a specific tumor marker resulted in no advantage, in the other types of tumors, the specific marker for each tumor identified correctly malignant effusions in 72 of 74 cases (97%). In fact, CEA was positive in 11 of 11 effusions induced by colorectal cancer; CA 19.9 in 28 of 30 gastric cancer effusions, while MCA and CA 15.3 were positive in breast cancer effusions (16/22 and 20/22). Finally, elevated AFP and PSA indicated hepatocellular and prostate cancer, respectively. In conclusion, in cancer patients with elevated effusion levels of specific tumor markers, the effusions could be considered of a malignant nature even without cytologically demonstrable tumor cells.

Consolidation biochemotherapy for patients with advanced nonsmall cell lung carcinoma responding to induction PVM (cisplatin, vinblastine, mitomycin-C) regimen. A phase II study.

BACKGROUND: The authors investigated a consolidation biochemotherapy program with subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN alpha) biologic response modifiers (BRM) in patients with advanced nonsmall cell lung carcinoma (NSCLC) with responsive or stable disease to induction chemotherapy. METHODS: Patients with proven, advanced, previously untreated NSCLC were entered into the study. Induction chemotherapy consisted of cisplatin, 120 mg/m2 intravenously (i.v.), on Day 1; vinblastine, 6 mg/m2 i.v., on Day 1; and mitomycin-C, 6 mg/m2 i.v., on Day 1 (PVM), every 3 weeks. Subsequently, patients with complete response (CR), partial response (PR), and stable disease (SD) received consolidation biochemotherapy with subcutaneous rIL-2, 3 MU/m2 twice/day, and rIFN alpha, 3 MU once/day, 5 days a week, starting 2 weeks after the second PVM course. After 3 and 6 weeks of BRM treatment, patients had a 14-day rest period to intercalate consolidating PVM courses. RESULTS: Seventy-seven patients were enrolled in the trial. After 2 PVM induction courses, 16 patients progressed and went off the study, whereas 61 patients were eligible for consolidation biochemotherapy. Among the 61 patients, 9 were not treated with BRM for several reasons, whereas 52 patients began biochemotherapy and were evaluable for toxicity. Furthermore, a few days after starting BRM, 9 patients discontinued therapy due to side effects; the remaining 43 patients received adequate treatment and were fully evaluable. In the 52 evaluable patients, the following BRM related toxicities were observed: World Health Organization (WHO) grade 2-3 fever in 85% of patients, asthenia in 71%, anorexia in 63%, and flu-like syndrome in 18.5%. PVM-related vomiting was present in 19% of patients. WHO Grade 3-4 myelosuppression, from both BRM and PVM (overlapping toxicity), was anemia in 16% of patients, leukopenia in 12%, and thrombocytopenia in 19%. There were three toxic deaths: two due to BRM-induced hypotension and one from pneumonia. In the 43 fully evaluable patients (23 PR and 20 SD after induction chemotherapy), after a median of 6 weeks of biochemotherapy (range, 3-16 weeks), we observed 5 of 20 patients achieving PR from SD, and 6 of 23 with confirmed PR. In these 11 patients, the median duration of response was 21 weeks (range, 7-80 weeks). Overall response improvement was 11.6% in the 43 patients and 6.4% in the 77 total enrolled patients. Median survival was 41 weeks (range, 15-173 weeks) in the 43 patients and 38 weeks (range, 1.4-173 weeks) in the 77 patients. CONCLUSIONS: In this study, biochemotherapy, when administered by this dose and schedule, did not offer substantial benefit although it caused significant toxicity.

Multimodal biochemical modulation of 5-fluorouracil by leucovorin, methotrexate, and interferon alpha in patients with advanced colorectal cancer.

A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i.v. on days 1-4; 400 mg/m2 5-fluorouracil i.v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i.v. on days 2, 3, 5, and 6. Interferon-alpha 2b at a dose of 3 million U was given i.m. daily for the 6 days of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence interval 2-28%): In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to be effective, as it results in severe toxicity.

The clinical impact of FEM regimen (5-fluorouracil, 4-epidoxorubicin and mitomycin-C) in advanced gastric cancer patients.

The activity of FEM regimen in metastatic gastric cancer patients was assessed in seventy-seven patients receiving, as palliative treatment, 5FU 600 mg/m2 i.v. on days 1, 8, 29, 36; epiADR 70 mg/m2 i.v. on days 1, 29; MIT-C 10 mg/m2 i.v. on days 1, 29. Cycles were repeated every 58 days. One patient achieved a complete response and 12 a partial response, resulting in an overall response rate of 16% (95% CI: 8% to 24%). Median remission duration was 6 months. Median survival time for all patients was 8 months. Side-effects were mild and principally in the form of leukopenia (three episodes grade III). Our results support the recent findings about the lack of effectiveness of this regimen. Although it is a safe and well tolerable chemotherapeutic combination, FEM regimen should not be recommended as routinary treatment for gastric cancer patients who are not eligible for clinical trials.

Recombinant human erythropoietin treatment in elderly cancer patients with cisplatin-associated anemia.

The efficacy of recombinant human erythropoietin (rHuEPO) on the increase in hemoglobin levels was assessed in patients with cisplatin (CDDP)-induced anemia older than 70 years. Furthermore, we compared the results obtained in this group of patients with those observed in other patients receiving rHuEPO for a CDDP-associated anemia with similar clinical features (chemotherapeutic regimen, primary tumor; CDDP cumulative dose) but of an age less than 70 years. Twenty patients older than 70 years with a CDDP-associated anemia (hemoglobin levels < 90 milligrams) received rHuEPO at the dose of 100 U/kg subcutaneously, three times a week. The control group consisted of 20 younger patients, anemic after CDDP chemotherapy, treated with rHuEPO. All patients were evaluable for response and toxicity. Hemoglobin concentrations showed a statistically significant increase after the 3rd, 6th and 9th week of therapy in both older (93.1 +/- 10.7, 103.5 +/- 8.2 and 102.7 +/- 8.2, respectively, vs. baseline, 84.6 +/- 4.9) and younger patients (95.3 +/- 11.7, 101.5 +/- 13.4 and 101.9 +/- 8.7, respectively, vs. baseline, 86.6 +/- 4.0). Furthermore, 30% of older patients required blood transfusions versus 35% of younger patients, with the mean unit of blood transfused per patient being 0.7 U in elderly and 0.65 U in younger patients. Treatment was well tolerated with no significant side effects. The CDDP-induced anemia seems to be corrected by rHuEPO also in elderly patients, without differences with respect to younger patients.

Oral escalating dose of cyclosporine-a combined with 4-epidoxorubicin in advanced colorectal-cancer - a phase-I study.

Multidrug resistance, a major factor in the resistance to drugs, can be reversed by cyclosporin A. It is generally given by intravenous route. The aim of the present study was to assess the possibility of achieving useful plasma levels, giving cyclosporin A orally in advanced colorectal cancer patients treated with 4-epidoxorubicin. Cyclosporin A was given orally twice a day, for four days. The starting study dose was 5 mg/kg. Dose in cohorts of 3 patients was escalated to 10, 15, 20, 30, 40 mg/kg if the previous dose was not able to determine the target blood level (2,000 ng/ml). Cyclosporin A blood levels were analyzed by a specific fluorescence polarization immunoassay method (TDx; Abbot Laboratoires, North Chigaco, IL). 4-epidoxorubicin was given at a fixed dose of 75 mg/m(2), every 3 weeks. None of the dose levels of cyclosporin A given orally produced the target blood level. Only two patients, receiving cyclosporin at a dose of 30 mg/kg, and two after a CsA dose of 40 mg/kg, presented blood levels higher than 1,000 ng/ml, but however, lower than 1,500 ng/ml. In conclusion, the oral route of administration of cyclosporin does not seem recommendable in order to reverse multidrug resistance because it is not able to produce sufficient plasma levels.

Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis.

Recently, a randomised study demonstrated the utility of oral cooling (cryotherapy) in the prevention of 5-fluorouracil (5FU)-induced stomatitis. In order to verify these results a confirmatory study, using identical treatment regimen, was initiated. 84 patients treated with a 5-FU-containing regimen were randomised to a control arm or to receive oral cryotherapy. End point evaluation was obtained by a global assessment of the physician's judgement and patients' description of mucositis severity graded 0-4. Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy (the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group, P < or = 0.05) and all the chemotherapeutic courses (the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group, P < or = 0.05). In conclusion, the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens.

Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo.

PURPOSE: To evaluate the effect of exogenous recombinant human erythropoietin (rHuEPO) on the increase of hemoglobin levels and on the transfusion requirements in patients with cisplatin (CDDP)-induced anemia, we performed a double-blind randomized trial with placebo. PATIENTS AND METHODS: One hundred patients with CDDP-associated anemia (hemoglobin level < 90 g/L) were randomized to receive either placebo (saline solution) or rHuEPO (100 U/kg body weight subcutaneously) three times per week. The end points of this study were the increase in hemoglobin levels to greater than 100 g/L after 3, 6, and 9 weeks and the effect on transfusion requirements. RESULTS: Ninety-nine of 100 patients were assessable for response and toxicity. In the rHuEPO arm, mean hemoglobin levels were statistically significantly increased after the third, sixth, and ninth weeks of therapy (101.1 +/- 9.0, 102.4 +/- 6.6, and 105.1 +/- 9.4 g/L, respectively) compared with the mean baseline value (86.3 +/- 6.2 g/L). In the placebo arm, there were no increases in mean hemoglobin levels at the third, sixth, and ninth weeks (81.0 +/- 5.2, 81.3 +/- 9.2, and 81.2 +/- 11 g/L, respectively) compared with the mean baseline value (87.3 +/- 5.2 g/L). Furthermore only 20% of patients required blood transfusions in the rHuEPO arm versus 56% of patients in the placebo arm (P = .01), with a mean units of blood transfused per patient of 0.30 in the rHuEPO arm and 1.8 in the placebo arm (P = .01). Treatment was well tolerated, with no significant side effects. CONCLUSION: CDDP-induced anemia is corrected by rHuEPO, which results in reduced blood transfusion requirements.

Cisplatin, 5-fluorouracil and interferon alpha 2b for recurrent or metastatic head and neck cancer.

On the basis of preclinical data suggesting the possibility of maximising the efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at 1,000 mg m-2 by continuous infusion for 5 days. Interferon alpha 2b was administered at the dose of 3 million U i.m. daily for 7 days, beginning the day before chemotherapy. Courses were repeated every 3 weeks. Two patients achieved a complete remission, six a partial response, 14 had stable disease and 12 progressed on therapy, for an overall response rate of 23% (95% confidence interval 10-36%). Median survival time was 5 months. Toxicity was severe. Stomatitis, diarrhoea and myelosuppression were the most common side-effects. Because of the poor response rate and the presence of severe toxicity, in our opinion further clinical trials in head and neck cancer should be attempted only after a better definition in preclinical studies of interactions among 5-fluorouracil, cisplatin and interferon.

Etoposide, leucovorin, 5-fluorouracil and interferon alpha-2b in elderly gastric cancer patients: a pilot study.

A total of 23 advanced gastric cancer patients older than 65 years received 500 mg/m2 5-fluorouracil i.v. on days 2-4, 120 mg/m2 vepesid i.v. on days 2-4, 150 mg/m2 6S-leucovorin on days 2-4, and 5 MU/m2 interferon alpha-2b on days 1-5, with cycles being repeated every 3 weeks. Toxicity was severe at an interferon (IFN) dose of 5 MU/m2; only one patient tolerated this dose. In 18 patients an IFN dose of 3 MU/m2 and in 3 other patients a dose of 4 MU/m2 could be given without producing toxicity. At an IFN dose of 5 MU/m2 the most common toxicities encountered were stomatitis (grade 4 in 1 patient and grade 3 in 12 patients), leukopenia (grade 4 in 1 patient and grade 3 in 5 patients), and thrombocytopenia (grade 3 in 3 patients). Two patients achieved a complete response and eight showed a partial response, resulting in an overall response rate of 45% [95% confidence interval (CI), 25%-64%]. The median survival was 7 months for all patients and 9 months for responding patients. In conclusion, without substantially increasing the toxicity, IFN can be added to the etoposide/leucovorin/5-fluorouracil combination, at a dose of 3 MU/m2. To verify the possible enhancement by IFN of the activity of this combination, a randomized trial is under way.

Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with placebo in patients receiving cisplatin.

Cisplatin-related diarrhea is a relatively common complication in the clinical management of cancer patients and until now no treatment for this condition has been identified. Octreotide has been reported effective in the treatment of 5-fluorouracil-related diarrhea. To assess the safety and efficacy of octreotide in controlling diarrhea caused by cisplatin, 43 patients who had already had diarrhea during the 24-hour period following a previous cisplating administration were randomized to receive either octreotide or placebo during the next cisplatin course. The patients given octreotide experienced less diarrhea (5 vs. 75%, p = 0.01). There were no side effects. We conclude that octreotide is more effective than placebo in controlling diarrhea following cisplatin chemotherapy.

Carboplatin associated anemia treated with subcutaneous erythropoietin - a pilot-study.

In nineteen patients with carboplatin-induced anemia (hemoglobin less than 90 g/l), recombinant human erythropoietin was administered subcutaneously three times a week on an outpatient basis. The initial dose was 50 Units/kg of body weight. If response was not achieved within 3 weeks, dose was increased to 75 Units/kg. Using the same criteria further escalations to 100 and 150 Units/kg were performed. If there was no response erythropoietin was terminated. Two patients obtained an increase of hemoglobin levels greater than 100 g/l, which was considered as a clinical response in this study, with a dose of 75 U/kg; eleven patients needed an erythropoietin dose of 100 U/kg and three a dose of 150 U/kg. The other three patients required hemotransfusions and were considered non responders. Hemoglobin increases occurred despite continuation of carboplatin chemotherapy. In conclusion, subcutaneous eryhtropoietin is effective and safe in the treatment of carboplatin-induced anemia.