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)?

Cure is possible by resecting colorectal isolated liver metastases. In non-resectable isolated colorectal liver metastases (CRLM), regional chemotherapy has been advocated to optimize the disease control in the liver in order to improve the results of the alternative, systemic chemotherapy. The drugs are delivered by means of hepatic artery infusion (HAI) via ports or pumps; pharmacological modifications of the hepatic arterial blood-flow-like HAI with starch microspheres or stop-flow and perfusion techniques were applied to improve HAI.

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.

Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being studied for adjuvant chemotherapy of curatively resected colorectal cancers. To evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual patient data (IPD) meta-analysis of randomized clinical trials was performed in Japan as an inter-trialist group study.

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.

To compare combination chemotherapy (CCT) versus melphalan plus prednisone (MP) as treatment for multiple myeloma.

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.

A collaborative overview, using individual patient data, has been performed to compare idarubicin versus daunorubicin or other anthracyclines, when used with cytosine arabinoside as induction chemotherapy for newly diagnosed acute myeloid leukaemia. There were 1052 patients in five trials versus daunorubicin, 100 in one trial versus doxorubicin, and 745 in one trial versus zorubicin. In the trials of idarubicin versus daunorubicin, early induction failures were similar with the two treatments (20% idarubicin v 18% daunorubicin: P = 0.4), but after day 40 the later induction failures were fewer with idarubicin (17% v 29%: P < 0.0001). Therefore complete remission rates were higher with idarubicin (62% v 53%; P = 0.002). Among remitters, fewer of the patients allocated to idarubicin relapsed (P = 0.008) but slightly more died in remission, leading to a non-significant benefit (P = 0.07) in disease-free survival. Overall survival in these five trials was significantly better with idarubicin than with daunorubicin (13% v 9% alive at 5 years; P = 0.03). There was a trend (P = 0.006 for remission rate) for the benefit of idarubicin over daunorubicin to decrease with increasing age. There were no significant differences in outcome in the small trial comparing idarubicin versus doxorubicin, or in the large trial comparing idarubicin versus zorubicin. The induction regimens based on idarubicin achieved, in the particular circumstances of the trials reviewed here, better remission rates and better overall survival than those based on daunorubicin.

To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer.

Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist.

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.