Weekly regimen of paclitaxel and carboplatin as first-line chemotherapy in elderly patients with stage IIIB-IV non small cell lung cancer (NSCLC): results of a phase II study.

Single-agent chemotherapy is the preferred treatment option in chemonaive elderly patients with advanced nonsmall-cell lung cancer (NSCLC). The role of combination chemotherapy in this setting is uncertain although several studies report satisfactory efficacy and safety using weekly paclitaxel and carboplatin (AUC=6) as first-line chemotherapy in elderly patients. It is still unclear which schedule of this regimen which could offer the best therapeutic index. The aim of this study was to evaluate the activity and tolerability of concomitant weekly administration of paclitaxel and carboplatin in untreated elderly patients with advanced NSCLC. From february 2005 to April 2008 36 consecutive elderly patients with advanced NSCLC were enrolled. Median age was 74 years (range, 70-83 years) and median ECOG PS was 1 (range, 0-1). patients received carboplatin (AUC=2) and paclitaxel 80 mg/m² on days 1,8 and 15 every 28 days. All patients were evaluable for efficacy and toxicity; a median of 4 cycles was administered. Twelve patients had partial response (33%; 95% C.I. 15,8-52,3%), 10 patients (28%) showed stable disease. The median time to progression (TTP) was 5.7 months (95% C.I. 3.1-8.6 months) with a median overall survival (MOS) of 9 months (95% C.I. 4.4-13.9 months). Toxicity was mild with no cases of febrile neutropenia; 5 patients (14%) developed grade 2 neuropathy. Our study confirms the substantial activity of weekly regimen of paclitaxel and carboplatin. Due to its favorable profile of toxicity this schedule could represent an interesting therapeutic option in selected chemonaive elderly patients with advanced NSCLC.

A phase II study on metastatic breast cancer patients treated with weekly vinorelbine with or without trastuzumab according to HER2 expression: changing the natural history of HER2-positive disease.

PURPOSE: To observe whether in pretreated metastatic breast cancer patients with HER2-positive disease vinorelbine plus trastuzumab can produce different overall response rate (ORR), time to progression (TTP), and overall survival (OS) from women with HER2-negative tumors treated with vinorelbine alone. METHODS: Between June 2000 and January 2004, 68 consecutive women were enrolled: 33 patients received vinorelbine (V) alone, while 35 patients were given trastuzumab plus vinorelbine (T+V) according to HER2 expression determined by immunohistochemistry. In tumors scored +2, HER2 gene amplification was determined by fluorescence in situ hybridization. RESULTS: In patients treated with V (HER2-negative tumors) the ORR was 27.3%, while in those given T+V (HER2 positive tumors) the ORR was 51.4%. The median duration of response was 8 months for women treated with V and 10 months for those who received T+V. Patients given T+V had a longer TTP (9 months) and OS (27 months) than those receiving V alone (6 months and 22 months respectively). Toxicity was mild in both groups. Concerning cardiotoxicity in T+V group, 7 patients (20%) had left ventricular systolic disfunction. CONCLUSION: Our data suggest that trastuzumab can change the natural history of HER2-positive metastatic breast cancer. In fact, when treated with trastuzumab, women with HER2-positive disease had better prognosis than patients with HER2-negative tumors. Conducting a formal phase III trial comparing vinorelbine alone vs vinorelbine plus trastuzumab in HER2-positive metastatic breast cancer women could be debatable.

Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer.

BACKGROUND: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer. The aim of this phase II study is to determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced non-pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three chemotherapy-naïve patients were enrolled. Capecitabine 2500 mg/m(2)/day was administered orally twice a day continuously for 14 days and oxaliplatin 120 mg/m(2) was administered as a 2-h infusion on day 1, repeated every 3 weeks. RESULTS: Forty-three patients were assessable for toxicity and 39 for clinical activity: the main toxicity was grade 3 or 4 diarrhea, which occurred in 28% of the patients. The response rates were 44% [95% confidence interval (CI), 29.3% to 59.0%] and 48.7% (95% CI 33.0% to 64.4%) (intention-to-treat and per protocol analysis, respectively). The median overall survival was 20 months (95% CI 12-28). CONCLUSIONS: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer; therefore, the capecitabine dose we utilized is probably too high. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. This combination may be preferable compared to a standard combination with infusional fluorouracil/leucovorin as it is more convenient and practical with similar efficacy. Thus, phase III trials are needed to clarify its role in the treatment of chemotherapy-naïve advanced colorectal cancer patients.

Salvage chemotherapy for advanced sarcoma patients: a single-institution experience survey.

There is no standard salvage chemotherapy for patients with recurrent sarcoma following a first-line chemotherapy. A few therapeutic options are available and of limited efficacy. The objective of this study was to determine the activity and toxicity of salvage therapies in advanced sarcoma patients in our experience. A retrospective analysis of 41 case records of patients with recurrent sarcoma treated at our division between May 1995 and October 2000 was conducted. Several different therapy regimens were employed: dacarbazine (DTIC) in 16 patients; carboplatin (CBDCA) plus gemcitabine (GEM) in 9 patients; ifosfamide (IFO) in 10 patients; other regimens in 6 patients. A total of 153 cycles of chemotherapy were delivered (median, 3 cycles). Among 38 evaluable patients, seven partial responses were obtained (RR 18.4%). Treatment-related responses were: 2/15 in DTIC group; 1/8 in CBDCA/GEM group; 3/9 in IFO group; 1/6 in other regimens. Stable disease was obtained in 10 patients. Median time to treatment failure and median survival time were 5 months and 4.5 months, respectively. The main treatment-related toxicities were hematologic and gastrointestinal. Most of salvage chemotherapies for recurrent sarcoma patients have an unacceptably high treatment failure rate and do not appear to offer any quality of life advantages. Future clinical trials with high dose ifosfamide seem appropriate even if the use of investigational new drugs and novel strategies in these patients should be considered.

Ifosfamide and epirubicin combination in untreated sarcomas: two treatment schedules.

BACKGROUND: The Epirubicin (EPI) and ifosfamide (IFO) combination has been widely tested in soft tissue sarcomas, even though the optimal schedule of drug administration has still to be defined. In this article, we reviewed the activity and the toxicity of two EPI- and IFO-based schedules in newly diagnosed sarcomas. MATERIAL AND METHODS: 22 patients (group A) received a 'concurrent' schedule of short-infusion IFO at total dose of 7.5-9 g/m(2) over 5 days plus iv bolus EPI at 90-120 mg/m(2)/cycle, repeated every 3 weeks. The other 22 patients (group B) received a 'sequential' schedule of dose-intense, continuous infusion IFO at a total dose of 14-18 g/m(2) for 2 cycles followed by bimonthly EPI at 120-160 mg/m(2)/cycle. Application of growth factors was planned for each course of treatment. RESULTS: Since 1994, 44 consecutive patients have been treated. The overall response rate was 35% with no significant differences between the two treatment groups in terms of response rate (group A: 33%, group B: 37%), time to progression (group A: 7 months, group B: 8 months), and overall survival (group A: 12 months, group B: 15 months). General tolerance to treatment was better in group A. Gastrointestinal symptoms occurred significantly more often with the sequential regimen. Severe hematologic toxicity was common but no toxic deaths were observed. CONCLUSIONS: Based on this limited experience, a concurrent schedule of EPI and IFO seems to be an appropriate management strategy in the front-line therapy of advanced sarcomas. Nevertheless, a randomized trial is warranted to define the optimal dosages to be used for further clinical trials.

[An ultrastructural research of pancreatic islets in sodium nitrite poisoned rabbits (author's transl)]. / Ricerca sull'ultrastruttura delle isole pancreatiche in conigli sottoposti ad intossicazione subacuta di sodio nitrito

Following a biochemical and histological study, the pathogenic effects of the sodium nitrite were investigated by the electron microscope. The vasodilator effect of the nitrite causes in the islets edema and dilatation of the sinusoids. We suppose that the increased afflux of blood could favour the secretion of granules till the exhaustion of cells. Moreover, the endoplasmic reticulum becomes more and more homogeneous and finally he loses its characteristic structure. We observed, at last, that the number of pancreatic islets in the poisoned animals is lower than in control animals.