Low dose-intensity docetaxel in the treatment of pre-treated elderly patients with metastatic breast cancer.

We evaluated the efficacy and toxicity profile of single-agent docetaxel administered in daily clinical practice at low-dose regimen in 37 pre-treated elderly patients with metastatic breast cancer previously exposed to chemotherapy. Docetaxel was employed by physician's preference according to a weekly (8 patients, 25-30 mg/m2 every 7 days), bi-weekly (19 patients, 40-50 mg/m2 every 14 days), or tri-weekly (10 patients, 75-100 mg/m2 every 21-28 days) schedule. The median age of patients was 70 yrs, and most of them (84%) had a good PS; visceral metastases were found in 26 patients. Twenty-five patients were pre-treated by two or more chemotherapy lines. Anthracycline or anthracycline/paclitaxel therapy was previously employed in 25 patients (67%). Median delivered dose-intensity of docetaxel was 21 mg/m2/week (range 11-32), without significant differences between the regimens used. Thirty-three patients were evaluable for response. Eight (24%) patients had objective responses (2 complete and 6 partial) to docetaxel, with a median duration of response of 18 months; 14 (42%) patients had stable disease lasting more than 6 months (median 10 months). Median overall time to progression was 6 months. Median overall survival was 16 months, with 1- and 2-year survival rates of 64% and 34%, respectively. Grade 3/4 toxicities were rare: leucopenia in 18% of patients, neutropenia in 13%, emesis in 8%, diarrhea in 5%, and mucositis in 5%. Severe fatigue was recorded in 4 patients. In conclusion, docetaxel, even when administered at low dose-intensity, demonstrated good disease control and toxicity profile. This approach provides an excellent alternative for pre-treated elderly patients with advanced breast cancer.

High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer.

BACKGROUND: The proportion of elderly within the general population is increasing and the incidence of colorectal cancer increases with age. Oxaliplatin and 5-fluorouracil (FU) combination is active in this disease. PATIENTS AND METHODS: This multicenter phase II study was designed to investigate feasibility, efficacy, activity of daily living (ADL) and instrumental activity of daily living (IADL) in elderly patients with metastatic colorectal cancer treated, as first-line chemotherapy, with a bi-fractionated oxaliplatin/5-FU based regimen. Treatment was oxaliplatin 45 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 and 22 h continuous infusion of 5-FU 600 mg/m2, all given intravenously on days 1 and 2, every 2 weeks. RESULTS: Seventy-eight patients were enrolled; median age was 75 years (range 70-85). Among 77 evaluable patients, we observed seven complete responses and 32 partial responses, for an overall response rate of 51% (95% confidence interval 40% to 62%). A stabilization of disease was observed in 25% of patients while 19 patients progressed. Canadian NCI grade 3/4 toxicities were: neutropenia in 32% of patients (febrile in two), diarrhea in 10%, mucositis in 4%, and fatigue in 4%. Sensory neuropathy was mild and occurred as grade 3 in 6% of patients. ADL and IADL scores did not change significantly during treatment. CONCLUSIONS: The bi-fractionated delivery of oxaliplatin plus 5-FU/leucovorin demonstrated high antitumor activity in elderly patients with advanced colorectal cancer. Splitting oxaliplatin administration might reduce incidence of severe neuropathy, although this has to be confirmed by further studies.

Factors predicting docetaxel-related toxicity: experience at a single institution.

We studied factors predicting docetaxel-related toxicity in 113 unselected patients with metastatic cancer treated under routine daily practice. Docetaxel was administered in either a weekly, bi-weekly or tri-weekly schedule. All patients received prophylactic dexamethasone. Twenty-six patients were aged 70 or more, and 28 (24.8%) had an ECOG performance status (PS) score > or = 2. Primary tumors were mainly in breast, lung, and stomach (58, 25, and 14 patients, respectively). Most patients had metastases at two or more sites and were heavily pretreated. NCI-CTC graded toxicities were mild. Grade 3/4 leucopenia and neutropenia occurred in 19.4% and 10.6% of patients, respectively, with febrile neutropenia in 2 patients. Severe nonhematologic toxicities were rare, except for asthenia (8 patients). Complete alopecia occurred in 26.6% of patients. A proportional-odds regression analysis demonstrated that the tri-weekly schedule and older age represented independent risk factors for all-grade leucopenia, whereas a poor PS for anemia. Primary tumor in breast, tri-weekly schedule, an abbreviated and low dose of corticosteroids premedication, and high duration and cumulative dose of docetaxel were factors predicting asthenia. Risk factors for alopecia and vomiting were tri-weekly schedule and high docetaxel cumulative dose, respectively. In conclusion, in daily clinical practice docetaxel toxicity may be correlated with factors related to patient, disease, and treatment characteristics. Taking into account these variables could be a first step toward individualizing treatment.

Serum tumor markers may precede instrumental response to chemotherapy in patients with metastatic cancer.

PURPOSE: Although serum tumor markers (STMs) are widely used in clinical practice, their predictive role for the response to anticancer treatment is still controversial. The correlation of CEA, CA 15.3, CA 19.9, CA 125 (only with peritoneal involvement) and NSE levels with imaging response and clinical benefit was investigated in 60 non-selected patients with metastatic epithelial cancers treated by single-agent docetaxel chemotherapy. METHODS: STM measurement was performed at baseline and subsequently every three to four weeks. We applied the WHO criteria to evaluate both STM and instrumental responses. Concordance analysis was performed by the Cohen Kw index, and the significance of the results was established using the Fleiss, Cohen & Everitt test. Qualitative interpretation of data was obtained with the Landis & Koch scale. Correlations of STM response with clinical benefit (PS or pain improvement) were evaluated by the chi-square test. RESULTS: The primary tumors included breast cancers (38 patients), gastrointestinal non-colorectal cancers (12 patients), and lung cancers (10 patients). An overall significant good degree of agreement was observed between STM and instrumental response (p < 0.0005). The degree of agreement for each marker was as follows: excellent for CEA (p < 0.0005) and CA 125 (p = 0.006), good for CA 15.3 (p < 0.0005) and CA 19.9 (p = 0.011). Restricted analysis for the correlation of each marker with primary tumor origin showed good prediction of radiological response for CA 15.3 and CEA in breast cancer patients (p<0.0005 for both), for CEA and CA 19.9 in gastrointestinal cancer patients (p = 0.01 and 0.04, respectively), and for CEA+NSE in lung cancer patients (p = 0.01). Conversely, STM response did not correlate significantly with the clinical benefit for the patients, both in terms of PS and pain improvement (p = 0.24 and p=0.42, respectively). CONCLUSION: This study showed STMs to be good predictors of tumor response. Although STMs cannot replace diagnostic imaging, in metastatic cancer they might be useful to optimize the timing of radiological re-evaluation in the palliative setting.

Treatment of malignant gliomas: a new approach.

The aim of this study is to describe the authors' experience with intra-arterial ACNU chemotherapy of malignant gliomas. The prognosis of cerebral malignant gliomas remains poor, whatever traditional therapy is applied. ACNU is a well tolerated nitrosourea with a strong antimitotic effect on neurogenic cells both in vitro and in vivo; this drug has enhanced efficacy when used at high concentrations, particularly as an intraarterial infusion. Seventy-six patients have been studied to date, 68 of whom are evaluable; these patients were treated by intra-arterial infusion of ACNU (100 mg/m2) every 6 weeks, with a mean of 2.5 courses per patient. The objective response (OR) was 28% and analysis of pretreatment factors revealed that survival was influenced by histological grade, other types of therapy applied, and age. In general IAC is well tolerated and the response and survival appear to be better than with systemic chemotherapy.

A multicentre, double-blind, randomised trial comparing ondansetron versus ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis.

The aim was to compare the efficacy of ondansetron and a combination of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis over three consecutive courses of chemotherapy. Cancer patients scheduled to receive for the first time cisplatin (>50 mg/m(2)) in combination with other cytotoxic agents, were recruited in a multicentre, randomised, double-blind study and treated with ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. Twenty-four hours after the start of chemotherapy, patients were randomised to treatment either with oral ondansetron 8 mg bd plus placebo on days 2-5 (group A) or with oral ondansetron 8 mg bd plus oral dexamethasone 8 mg bd on days 2-3, and 4 mg bd on days 4 and 5 (group B). Two hundred and thirty-six cancer patients were recruited into the study. Complete protection from delayed vomiting/nausea in group A and group B was Obtained in 50/39% and in 63/42% of patients, respectively in the first course; in 55/34% and in 64/40% in the second and in 49/31% and 60/37% in the third. Logistic regression analysis reveals a statistically significant difference in incidence of emesis between the combination of ondansetron plus dexamethasone and ondansetron alone (P<0.05). The same model, however, shows no difference in incidence of nausea between the two treatment regimens. Ondansetron plus dexamethasone reduces the risk of delayed emesis following cisplatin chemotherapy as compared to ondansetron alone.

[Chemotherapy of intestinal carcinomas]. / Chemioterapia dei carcinomi intestinali.

It is not easy to weigh up therapeutic and toxic effects in the medical treatment of intestinal cancer. The number of drugs that have demonstrated certain activity in these forms is extremely limited, only 5 FU being definitely active and even this only in a small percentage of patients. 5 FU produces remission in some 20% of cases. It is highly probable that prophylactic treatment with 5 FU increases patient survival as reported by Regelson and other workers, but the resulting damage (hepatic, bone marrow, immunodepression, etc.) must also be assessed and the risk of a second neoplasia should not be forgotten. The personally used association of 5 FU and cyclophosphamide has proved active at least to the same extent as 5 FU alone, while toxic effects were not particularly important. Brilliant but unfortunately temporary results can be obtained by peritoneal PTC in peritoneal carcinomatosis. Good results with respect to the pain symptom have been obtained by associating 5 FU with radiotherapy in non-operable intestinal tumours.

[Use of deoxyribonuclease in the therapy of the neoplastic patient]. / Sull'uso della desossiribonucleasi nella terapia del malato neoplastico

The anti-inflammatory actvity of desoxyribonuclease has been demonstrated on a number of occasions. It has been suggested that its particular features may mean that it possesses an antineoplastic action, especially if employed in asociation with radiation or chemotherapy. The drug, which depolymerises DNA, was administered for 15-60 days [ 1 million U. on alternate days] over a period of 1 yr. in a series of 99 patients, with or without radiation or chemotherapy. No evidence of its antineoplastic activity was obtained, though the anti-inflammatory effect was distinctly observed. Quickly reversible signs of intolerance were noted in about 4% of the series.

Anxiety therapy in the neoplastic patient.

A clinical study was carried out in 73 neoplastic patients suffering from anxiety and other emotional upsets to assess the effectiveness and tolerance of lorazepam. Patients were given individualised daily doses ranging from 1.5 mg to 3 mg lorazepam for 15 to 60 days. Results, as assessed by the response of anxiety, tension, erethism and insomnia, showed that only 4 (5%) patients failed to obtain some relief. There was complete disappearance of all symptoms in 29 (40%) after 15 days, relief of at least one major symptom and reduction in the others in 27 (37%), and slight reduction in one or more symptoms in 13 (18%) patients. Side-effects were minimal and disappeared within a few days with continued treatment.

Treatment of neoplasia of the bladder with topical application of a synthetic peptide complex preparation: preliminary results.

Preliminary results are reported on the endo-vesical use of a complex of synthetic peptides ('Peptichemio') in 15 patients suffering from bladder neoplasia who were judged to be beyond surgery or radiotherapy. The agent was introduced into bladder in 20 mg doses diluted in 50 ml of 5% glucose and retained for approximately 30 minutes. Treatment was repeated every 5 to 7 days. The disappearance of the neoplastic mass in 13% of the cases and its reduction in a further 53% encourage the continued use of the preparation in local regional therapy of bladder neoplasia, and the findings help to establish treatment times and doses. For the moment, the authors recommend increasing the interval between treatments to 10 days or more once the neoplastic mass has been reduced or disappeared.