Vinorelbine-based chemotherapy in hormone-refractory prostate cancer.

BACKGROUND: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer. In this phase II study, the combination of Vinorelbine with 5-Fluorouracil and folinic acid (FLN regimen) was evaluated in patients with progressive or resistant disease after hormone therapy. PATIENTS AND METHODS: Thirty-four patients were treated with Vinorelbine at a dose of 20 mg/m2 intravenously (i.v.) on days 1 and 3, folinic acid (FA), 100 mg/m2 i.v. and 5-Fluorouracil (5-FU), 350 mg/m2 i.v. as a short infusion on days 1 to 3. The therapy was given in an out-patient setting, every 3 weeks. RESULTS: All of the 34 eligible patients were evaluable for toxicity and 30 for activity. A total of 127 cycles was administered (91% at full dose). Among thelS5 patients with measurable disease, four had a partial response (26.6%; C.I. 95%, 28.3% to 65.7%) and four achieved stable disease. In 14 patients (47%) a clinical benefit was documented. Six out of 15 patients with bone-only involvement had stable disease (40%). The median duration of stabilization and partial response was 16 weeks (range 4-24 weeks). The most common toxicity was hematological: Grade 4 (NCI-CTC scale) in five patients at re-cycle. Other toxicities were of low incidence and easy to manage. CONCLUSION: The encouraging results obtained with the FLN regimen in terms of clinical benefit and its predictable and manageable toxicity support the palliative role of this chemotherapeutic strategy in hormone-refractory prostate patients.

Phase I and pharmacologic study of weekly gemcitabine and paclitaxel in chemo-naïve patients with advanced non-small-cell lung cancer.

BACKGROUND: Gemcitabine (GEM) and paclitaxel (TAX) are active, non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performed a phase I study to determine the maximum-tolerated dose (MTD), antitumor activity and pharmacokinetics of GEM and TAX given weekly in chemo-naïve patients with advanced NSCLC. PATIENTS AND METHODS: Escalating doses of GEM (800-2000 mg/m2) and TAX (60-100 mg/m2) were administered on days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasma pharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. RESULTS: Dose-escalation was discontinued in absence of MTD because of increased cumulative toxicity leading to dose modification or treatment delay at levels 6 and 7 (TAX 100 mg/m2 plus GEM 1750 and, respectively, 2000 mg/m2). Hematological toxicity included grade 4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycle and febrile neutropenia in three cycles. Maximal non-hematological toxicity was grade 3 elevation in serum transaminases and grade 2 neuro-sensory toxicity in 8% and 5% of cycles, respectively. At the two higher dose-levels a non-linear pharmacokinetics of GEM was observed with a remarkable variability of Cmax and AUC. No pharmacokinetic interactions were reported. Objectives responses were seen at all dose levels, with an overall response rate of 43% (95% confidence interval (95% CI): 25.5%-62.6%) in 30 evaluable patients. CONCLUSIONS: The weekly administration of GEM and TAX is very well tolerated, and has shown promising antitumor activity in NSCLC. In view of the cumulative toxicity and of the pharmacokinetic profile of GEM, doses of 1500 mg/m2 of GEM and 100 mg/m2 of TAX are recommended for phase II studies.

Palliative care in Italy: the current situation.

Palliative care was initiated in Italy towards the end of the 1970s, mainly through the efforts of Professor Ventafridda and his colleagues. This article describes some of the most important steps made in this country to gain widespread acceptance for the principles and practice of palliative care. After about 15 years the Italian situation is still confusing. While some Regions have made progress, others are far from reaching even minimal goals. The efforts of many charities and of the Italian Society for Palliative Care and the Italian School for Palliative Medicine, have been huge, but still not sufficient to promote widespread involvement of the National Health Authorities. In the absence of clear Regional and central laws, the recent changes in the Italian health system combined with increasing financial difficulties threaten the advances already made.

Side effects of morphine administration in cancer patients.

According to the World Health Organization (WHO) guidelines, oral morphine is the first choice drug for treating moderate to severe cancer-related pain. The fear of the side effects caused by this drug and the scarce information about prevention and management of these effects are the main reasons for the underuse of morphine. The aim of this paper is to provide a review of the literature on the side effects most frequently present both in the titration phase and during chronic administration of oral morphine and to describe the appropriate treatment.

A clinical study on the use of codeine, oxycodone, dextropropoxyphene, buprenorphine, and pentazocine in cancer pain.

The authors report a prospective study on 944 cancer pain patients treated with one of the following opioids: codeine, oxycodone, dextropropoxyphene, buprenorphine, and pentazocine. Level of analgesia, duration of treatment, side effects, and drop out were evaluated for each drug. Twenty-four percent of the patients still benefitted from treatment at the fourth week of study, even if high drug dosages were not used. Pentazocine did not show an evident analgesic effect during the first 2 wk of treatment. The other opioids were found to be valid therapeutic instruments for chronic cancer pain control in a limited number of patients.

On the significance of Lhermitte's sign in oncology.

We present three cases of Lhermitte's sign out of twenty consecutive cases of epidural spinal cord compression due to metastatic cancer. The three patients were diagnosed with epidural thoracic compressions. The literature on Lhermitte's sign is reviewed with emphasis on the differential diagnosis of this symptom in oncological patients.

Pain treatment in cancer of the pancreas.

Pancreatic cancer remains an important cause of suffering among oncologic patients. Due to the current poor response to specific therapies, a palliative approach represents the main treatment for this kind of tumour. The authors present the results of a prospective study performed on 41 patients treated according to the World Health Organization guidelines for cancer pain relief; 21 of them were treated by neurolytic coeliac blockade as well. Results, even if not comparable between the two groups, show that this neurolytic technique can play an important role in palliative treatment, on condition that it is part of a multimodal continuing care system.

Clinical observations on controlled-release morphine in cancer pain.

The authors report the data from two studies on the use of controlled-release morphine sulphate tablets for cancer pain relief. This preparation allows just two administrations per day, in comparison with immediate release oral aqueous morphine solution. The first study, a randomized trial carried out on 70 patients suffering from advanced cancer pain, evaluated the analgesic efficacy and side effects of this drug. The second, an open study of 113 patients, assessed analgesic efficacy, incidence of side effects, and the effects of age on dose. The analgesia provided by controlled-release morphine administration proved to be superimposable to those of the oral aqueous morphine solution. Moreover, the use of controlled-release morphine was associated with a statistically significant reduction of some side effects. Ninety-one percent of patients needed controlled-release morphine every 12 hr, while 9% required it every 8 hr.

Oral complications in patients with advanced cancer.

Disturbances caused by lesions of the oral cavity play an important part in the alteration of the quality of life of cancer patients. The main complications affecting the oral cavity are infections (fungal, viral, bacterial), neutropenic ulcers, drug-induced stomatitis, dry mouth, and taste alteration. Most of the information available about these entities has been acquired in the cancer patient without advanced disease. The little known about the epidemiology and physiopathology of such lesions in the advanced phase of cancer is presented and approaches to management are suggested.

Issues in symptom control. Part 4. Oral complications in patients with advanced cancer.

Disturbances caused by lesions of the oral cavity play an important part in the alteration of the quality of life of cancer patients. The main complications affecting the oral cavity are infections (fungal, viral, bacterial), neutropenic ulcers, drug-induced stomatitis, dry mouth, and taste alteration. Most of the information available about these entities has been acquired in the cancer patient without advanced disease. The little knowledge about the epidemiology and physiopathology of such lesions in the advanced phase of cancer is presented, and approaches to management are suggested.