To perform a meta-analysis to estimate the efficacy of quinolone antibiotics in preventing infections, fevers, and deaths among cancer patients neutropenic following chemotherapy.

In a prior Cancer and Leukemia Group B (CALGB), 16% of a small cohort of patients with extensive small call lung cancer who had failed to obtain a complete remission with chemotherapy did obtain a complete remission after therapy with interleukin-2 (IL-2). In this current trial, 10 patients with extensive small cell lung cancer who had had no prior therapy were treated with subcutaneous IL-2 as induction therapy and then standard chemotherapy with etoposide/cisplatin. Only one patient experienced an objective response to the IL-2 administered prior to chemotherapy. The factors governing response to IL-2 in the first trial but not in this trial are discussed.

The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU.

This meta-analysis was conducted to compare the effects of single agent versus combination chemotherapy on response rate, toxicity, and survival of patients with advanced nonsmall cell lung carcinoma (NSCLC).

Several randomized clinical trials in chronic myeloid leukemia (CML) have reported better patient survival with interferon alfa (IFN alpha) than with standard chemotherapeutic agents, such as busulfan or hydroxyurea. However, the size and persistence of this survival benefit is uncertain. Our aim was to assess these reliably, both overall and in particular patient subgroups.

P-glycoprotein (gp170; encoded by the MDR1 gene [also known as PGY1]) is a membrane protein capable of exporting a variety of anticancer drugs from cells. MDR1/gp170 expression has been studied in breast cancer, but the prevalence of this expression and its role in breast tumor drug resistance are unclear.

Gemcitabine is a novel anticancer agent showing activity with relatively mild toxicity across a range of solid tumors including non-small cell lung cancer (NSCLC). In studies using similar doses and schedules, consistent response rates of around 20% were recorded in NSCLC. In an integrated safety study using data from 360 patients with NSCLC, gemcitabine exhibits a mild safety profile for such an active drug. Hematological toxicity is mild and short lasting, and the level of infection associated with this degree of myelosuppression was low. Mild transaminase elevations occurred frequently but were not progressive or dose limiting. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting were mild, rarely dose limiting and generally well controlled with standard antiemetics. Mild flu-like symptoms were experienced in a small proportion of patients and rarely resulted in discontinuation. Where edema or peripheral edema were experienced, there was no evidence of any association with cardiac, hepatic or renal failure. Hair loss was rare and there was no grade 4 alopecia. In conclusion, gemcitabine is a promising new agent in the treatment of NSCLC. Its mild toxicity which is non-overlapping with other cytotoxics has prompted investigation into its use in combination with other chemotherapy regimens.

Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response.

Systemic delivery of cytotoxic drugs yields relatively low doses in the liver, a major site of recurrence for colorectal cancer. Giving chemotherapy by means of continuous portal vein infusion (PVI) into the liver during the immediate postoperative period may improve therapeutic efficacy.

Gemcitabine is active against non-small cell lung cancer (NSCLC), with single-agent response rates of 20% or more in previously untreated patients. Its mild toxicity profile suggests that it should be well tolerated by older patients. To assess the impact of age on the efficacy and tolerance of gemcitabine, the results of four phase II trials of single-agent gemcitabine for the treatment of NSCLC were analyzed retrospectively. Starting doses for gemcitabine ranged from 800 to 1,250 mg/m2/wk, and in all studies gemcitabine was administered weekly for 3 weeks followed by a 1-week rest period. Response rates, toxicity, and dose delivery were compared for two age groups, less than 65 years (255 patients) or > or = 65 years (105 patients). The pretreatment characteristics for both patient groups were well balanced. Overall response rates were 16% and 24% for the younger and older patients, respectively (P = .072). Median survival and 1-year survival rates were 8.1 months and 27% and 9.1 months and 36%, respectively, for patients aged less than 65 years and > or = 65 years. Hematologic and nonhematologic toxicities were similar for both age groups. The number of cycles associated with dose reductions or dose omissions and the mean number of treatment cycles administered were also similar. In summary, gemcitabine is active and well tolerated in elderly patients with NSCLC, and is a promising new alternative for the treatment of this patient population.

Ten years after it was demonstrated in the ferret that cisplatin-induced emesis could be blocked by the selective 5-HT3 receptor antagonist MDL 72222, 5-HT3 receptor antagonists have become routine anti-emetic agents for chemotherapy-induced emesis. However, although in association with highly emetogenic, mainly cisplatin-containing regimens, the use of these agents is well justified, the net benefit of 5-HT3 receptor antagonists in association with moderately emetogenic regimens has not been that well clarified. Here, we present an overview of 30 randomised studies comparing 5-HT3 antagonists with the conventional anti-emetics in the prophylaxis of acute vomiting induced by cytotoxic chemotherapy. A meta-analysis showed that 5-HT3 antagonists reduce the risk of acute vomiting in comparison to conventional anti-emetics both with cisplatin treatments (15 trials; odds ratio 0.60; 95% confidence interval 0.51-0.70) and with moderately emetogenic treatments (11 trials; odds ratio 0.47; 95% confidence interval 0.39-0.58). The risk of acute vomiting seems to be further reduced when 5-HT3 antagonists are combined with dexamethasone.

Because of the predictability of significant emesis after its use, cisplatin serves as the standard emetic stimulus for trials of antiemetic drugs. To define better the incidence, severity, and pattern of emesis that follows cisplatin, facilitate the testing of new agents, and obviate the need for further placebo-controlled trials for this indication, individual patient data were compiled from completed studies with placebo antiemetics and cisplatin.

Colorectal cancer is the second most common cancer in the Western world. Nearly 6 out of 10 patients with colorectal cancer have or will have metastasis, and among patients with advanced disease, the liver is the most common site involved (in up to 70% of patients). Chemotherapy of advanced CRC was long considered as ineffective. Recently, however, chemotherapy has made great strides: a number of successful regimens have been reported especially since 1990. The first randomized trials showing a significant extension of survival in patients treated by chemotherapy as compared to those receiving only supportive care were published in 1992 and 1993. This article provides an up-to-date overview of palliative chemotherapy for metastatic colorectal cancer: tumor reduction is two times greater when 5FU is administered in combination with folinic acid or with Methotrexate than when it is administered alone. According to some studies, these combinations may also significantly improve the duration and quality of survival. Two recent controlled studies comparing systemic chemotherapy with supportive care showed a significant improvement in the duration of survival and a study in asymptomatic patients indicated a significant extension of the duration of the symptom-free period. Hepatic intra-arterial chemotherapy significantly prolongs survival but toxicity is high. Further clinical testing is needed to evaluate new agents, improve tolerance to treatment, and evaluate chemotherapy as a bridge to surgery for patients with initially inoperable metastasis.

To optimize fotemustine chemotherapy, the authors considered how to combine independent Phase II trials to predict the risk of first occurrence of severe toxicity as a function of initial patient characteristics.

The effects on long-term outcome in childhood acute lymphoblastic leukaemia (ALL) of the duration and the intensity of maintenance chemotherapy need to be assessed reliably. With this objective the Childhood ALL Collaborative Group coordinated a worldwide overview of all randomised trials that began before 1987.

Adjuvant tamoxifen for early breast cancer provides an improvement in relapse-free (RFS) and overall survival (OS), especially for older women. We carried out a meta-analysis to find out whether the benefit of adding chemotherapy to tamoxifen outweighs its costs in terms of toxic effects for postmenopausal patients.

Standard meta-analytical and pharmacoeconomic techniques were used to study the clinical effectiveness and the cost-effectiveness ratio of the prophylactic (or pre-emptive) administration of G-CSF to patients with small cell lung cancer treated with conventional myelosuppressive cytotoxic chemotherapy. In the first part of our study, we conducted a meta-analysis of the randomized clinical trials evaluating G-CSF for this clinical indication. Three trials were identified by our literature search and were included in the meta-analysis (overall number of patients = 606). The end-points for evaluating G-CSF included mortality from infection and the cumulative incidence of neutropenic fever over six cycles of chemotherapy. The results of our meta-analysis demonstrate that prophylactic G-CSF did not affect mortality but significantly reduced the incidence of neutropenic fever from 68.3% to 38.7% (pooled odds ratio = 0.29, 95% CI: 0.21-0.40; P < 0.001). In the second part of our study, we carried out a pharmacoeconomic analysis to estimate the cost-effectiveness ratio of pre-emptive G-CSF (i.e. the 'average' cost associated with the prevention of an episode of neutropenic fever). This cost-effectiveness ratio was US$ 14,372 using the Italian price of the drug converted into dollars, or US$ 41 088 using the US price. Finally, we estimated the revenue-neutral price of G-CSF based on American data of the cost-of-illness. The price ranged from US$ 395 to US$ 569 per cycle, a figure higher than the value (US$ 150) previously reported in the literature.

Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear.

Using the technique of meta-analysis, we aim to illustrate the potential benefit, or lack of it, in adding chemotherapy to locoregional definitive treatment in a prospective randomized setting.