Innovative techniques in the field of artificial intelligence could help to resolve several methodological problems. A model taking into account all the parameters involved in a therapy can foresee the results of each type of treatment or therapeutic protocol on patients at different stages of a disease. We used a Computer Decision Support System in order to verify the reliability and efficacy of this method on chemotherapy of colorectal carcinoma.

Fluconazole is used widely for fungal prophylaxis. Although studies with bone marrow transplantation (BMT) recipients clearly showed the usefulness of oral fluconazole, results of the studies in neutropenic patients other than BMT recipients have been inconsistent. Therefore, the authors performed a meta-analysis to evaluate the efficacy of fluconazole prophylaxis during chemotherapy-induced neutropenia.

To synthesize the available randomized evidence on the efficacy of dexamethasone when used for protection against acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic cancer chemotherapy.

Chemotherapy is the backbone of small-cell lung cancer therapy. However, optimal drug combinations and schedules remain to be defined and there is hitherto no world-wide accepted standard regimen. Cisplatin, an alkylating agent with high putative toxicity is currently widely used although its effectiveness in this disease has not been established firmly. We conducted a meta-analysis of published data reporting trials randomizing a cisplatin-containing regimen versus a regimen without this alkylating agent in order to determine possible differences in survival response and toxicity. Nineteen trials have been identified in medical literature (4054 evaluable patients). Ten trials randomized patients to receive a cisplatin-etoposide regimen versus a regimen without any of these two drugs. A subgroup analysis was, therefore, carried out in the nine remaining trials that randomly allocated patients between two regimens differing in the absence or presence of cisplatin, whereas etoposide was given (or not given) in both arms (1579 evaluable patients). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death and the increase in probability of being responders to chemotherapy. There was no significant difference between the cisplatin-containing regimen and the regimen without this drug when the risk of toxic-death was taken into account with respective probabilities of 3.1 and 2.7% (NS). Patients randomized in a cisplatin-containing regimen had an increase in probability of being responders with an OR of 1.35, 95% confidence interval (CI) of 1.18-1.55; P < 10(-5) corresponding to an increase of objective (partial plus complete) response rate from 0.62 to 0.69 (a result taking into account a significant heterogeneity). Patients treated with a cisplatin-containing regimen benefited from a significant reduction of risk of death at 6 months and 1 year with respective OR 0.87, 95% CI 0.75-0.98, P = 0.03, and or 0.80, 95% CI 0.69-0.93, P = 0.002 (no statistical heterogeneity). This corresponded to a significant increase in the probability of survival of 2.6% and 4.4% at 6 months and 1 year respectively. The meta-analysis restricted to the subset of nine trials without etoposide treatment imbalance reached similar conclusions. A cisplatin-containing regimen yields a higher response rate and probability of survival than does a chemotherapy containing others alkylating agents without a perceptible increase in risk of toxic-death.

To estimate the magnitude of benefit of chemotherapy in prolonging survival for patients with metastatic colorectal cancer, a meta-analysis of randomized controlled trial was performed. A systematic search was performed to identify randomized trials comparing chemotherapy with observation or supportive care alone. Trials were assessed for quality of reporting, publication bias and heterogeneity. Relative risks for outcomes from published data were pooled using a random-effects model. Seven trials with 614 patients were included. All trials used fluoropyrimidine-based chemotherapy, through a variety of routes and schedules, including intravenous, intra-portal and hepatic arterial infusion. Compared with the 'no-chemotherapy' arm, chemotherapy significantly reduced 1-year mortality (risk ratio 0.69; 95% confidence interval (CI) 0.60-0.81, P < 0.00001). The mortality at 2 years was not significantly different (risk ratio 0.93; 95% CI 0.87-1.00, P = 0.053). Between-trial comparisons demonstrated benefit with a variety of routes and schedules. Chemotherapy significantly prolongs 1-year survival for patients with metastatic colorectal cancer, and should be offered to those with good performance status.

Patients with advanced solid tumors may be included in phase I clinical trials. In such studies, the benefit expected is generally lower than the likelihood of toxicity and may even be non-existent if the patient's life expectancy is too short. This study was performed to identify prognostic variables for toxicity and survival in patients who participate in phase I clinical trials.

To compare luteinizing hormone-releasing hormone (LHRH) agonists with orchiectomy or diethylstilbestrol, and to compare antiandrogens with any of these three alternatives.

The purpose of this study was to describe the patterns of cancer-related fatigue (CRF) and vigor in patients receiving chemotherapy or radiation therapy. Five studies that measured fatigue and vigor with the Profile of Mood States were used to describe the pattern of CRF and vigor during and after both types of treatment. Repeated-measures ANOVA was used to determine differences over time in each study. Results demonstrate different patterns of CRF for patients receiving chemotherapy and radiation therapy. Chemotherapy-related CRF peaks in the days after chemotherapy, whereas radiation therapy-related CRF gradually accumulates over the course of treatment. The CRF associated with both forms of treatment gradually declines over time. The prevalence, intensity, and persistence of CRF during treatment and for months after treatment is complete make this symptom one that cannot be ignored.

A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)-based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis.

Meta-analysis of all clinical data was conducted to compare toremifene 40-60 mg/day (TOR) with tamoxifen 20-40 mg/day (TAM) in postmenopausal women with estrogen receptor (ER) positive or ER unknown advanced breast cancer and assess factors predicting treatment outcome. Data from five randomized parallel group studies (all studies) were combined. Efficacy variables were the response rate in all studies and also the time to treatment failure and survival in the three major studies (pivotal studies). Of the 1421 patients, 725 received TOR and 696 TAM. Response rates were 24.0% and 25.3%, respectively (p = 0.675) with 95% confidence interval (95% CI) for the difference -5.3 to 3.4. Of the 1157 patients in the pivotal studies, 75% had progressed and 50% expired. Median treatment times were 4.9 months in TOR and 5.3 months in TAM groups (p = 0.762, hazard ratio 0.98 with 95% CI 0.87-1.11). Median survival times were 31.0 (TOR) and 33.1 (TAM) months (p = 0.758, hazard ratio 0.98 with 95% CI 0.83-1.15). All results are consistent with the criteria of statistical equivalence between TOR and TAM. More patients in TAM (20%) than in TOR (14%, p = 0.007) discontinued the treatment prematurely but overall the treatments were well tolerated. As the treatments were equally effective all data were analyzed together for predictive factors. High tumor ER concentration, long disease free time, soft tissue metastases, few metastatic sites, and good performance status all independently predicted longer survival (p<0.001). Previous adjuvant tamoxifen predicted shorter survival (p = 0.008). Objective response to treatment or disease stabilization for at least 12 months both predicted prolonged survival (p = 0.001). TOR 60 mg/day and TAM are equally effective and well tolerated in the treatment of advanced breast cancer in postmenopausal women. Probability of survival may be predicted based on patient characteristics and on the initial response to the treatment.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.

Paclitaxel was the first identified member of a new class of anticancer drugs known as the taxanes. This compound has significant single-agent activity against a number of solid tumors including nonsmall cell lung cancer (NSCLC). In the first-line setting, single-agent paclitaxel has been studied on a number of different schedules and dose levels. Initial studies were done on the 24-h infusion schedule with doses of 200-250 mg/m2. Response rates were 21%-24%. Median survival ranged from six to nine months with one-year survival rates of 38%-42%. The major toxicity of this infusion schedule was myelosuppression, mainly neutropenia. Subsequent single-agent studies employed shorter infusion durations (three hours), with doses ranging from 175-225 mg/m2. The cumulative experience of the 3-h infusion schedule shows an overall response rate of 28.5% with median survival of 6-11 months and a one-year survival of 37.5%. Similar results were obtained in the one study examining the 1-h infusion schedule with doses ranging from 135-200 mg/m2. The major toxicities of the shorter infusion schedule include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Weekly administration of paclitaxel also showed significant activity in advanced, metastatic NSCLC. Overall response rates have ranged from 30%-56% in the phase I/II setting with one-year survival rates of 42%-53%. A recently completed phase III trial comparing single-agent paclitaxel at 200 mg/m2 over three hours every three weeks to best supportive care (BSC) in advanced or metastatic NSCLC has shown a survival advantage for the single-agent paclitaxel arm (median survival 6.8 months for paclitaxel versus 4.8 months for BSC, p = 0.045). An ongoing phase III trial is comparing single-agent paclitaxel to the combination of carboplatin and paclitaxel (CALGB 9730) in advanced, metastatic NSCLC. Paclitaxel has also been studied in the second-line setting. Infusion schedules have ranged from 1 h, 24 h and 96 h on an every-three-week schedule. Weekly paclitaxel has also been evaluated in the second-line setting. Although the overall experience is limited, response rates have ranged from 0%-38%. The overall role of single-agent paclitaxel in prolonging survival and improving quality of life remains uncertain in this setting. The cumulative experience of single-agent paclitaxel in advanced, metastatic NSCLC suggests that it is a highly active cytotoxic agent in this setting. The consistent finding of a 35%-40% one-year survival rate is notable. The major toxicities include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Given the overall activity and impact on survival along with an acceptable toxicity profile, single-agent paclitaxel warrants comparison to other active agents and combination regimens in advanced, metastatic NSCLC.

The disappointing results of chemotherapy in glioblastoma might be caused by the choices of agents, which mostly include nitrosurea. We compared the in vitro efficacy of chemotherapeutic agents, developing a method to summarize published data.

Is there a role for the use of gemcitabine in the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)?

Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States. Accumulating evidence indicates that postmenopausal hormone therapy may reduce the risk of colorectal cancer in women.

Owing to the wide spread perception of a possible benefit from paclitaxel in the second-line situation the Nordic Gynecologic Oncology Group (NGOG) conducted two prospective phase II studies of paclitaxel single agent treatment (175 mg/m2, three-hour i.v. infusion with standard pre-medication every third week) in patients with relapsing or progressing epithelial ovarian cancer following platinum.

A meta-analysis of 55 prospective randomized clinical trials including more than 37,000 patients has analyzed the effectiveness of tamoxifen in the treatment of breast cancer. Standard treatment consists of 20 mg tamoxifen daily for 5 years in patients with either a positive estrogen receptor or a positive progesterone receptor status. This treatment achieves a 50% improvement of the 5-year relapse-free survival and a 28% improvement of the overall survival. Tamoxifen is effective in lymph node-negative and lymph node-positive patients as well as in premenopausal and postmenopausal women. The combination of chemotherapy with hormonal treatment is even more effective and brings a further improvement of survival of 50%. In addition, tamoxifen reduces the number of contralateral breast cancer cases to 50%, but increase the occurrence of endometrial cancers from 1.2/1,000 breast cancer patients within 10 years to 4.4/1,000 women. In conclusion, tamoxifen 20 mg daily for 5 years is the standard treatment of hormone receptor-positive breast cancer patients.

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.