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In the Netherlands, cancer will remain a significant issue in health care according to a signalling commission of the Dutch national cancer fund (Nederlandse Kankerbestrijding/Koningin Wilhelmina Fonds). If smoking would be abandoned, the incidence of lung cancer would drop dramatically. The role of food in carcinogenesis appears to be much less than was earlier believed. Chemoprevention will also have very limited influence on cancer incidence. Attempts at early diagnosis of cancer have been so far successful only in patients with breast cancer over 50 years of age and in cervical cancer. More effective therapies for cancer are urgently needed. The cost-effectiveness of adjuvant chemotherapy in breast cancer and colon cancer is unfavourable. Determination of better prognostic factors may reduce the number of patients who unnecessarily undergo this treatment. New anticancer drugs tend to be very expensive and this lays a heavy burden on health care budgets. Efficacy of new treatments needs to be compared with established ones in randomized trials before reimbursement can be granted.

The development of new anticancer agents is becoming an increasingly complex task which is often beyond the capabilities of a single institution or company. To ensure fast, efficient, high-quality drug development, good coordination and collaboration are essential prerequisites. In this paper, the Dutch national drug development program is described as an example and placed in the perspective of Europe-wide efforts. Since knowledge of new molecular targets and biological approaches by which the malignant growth of cells can be stopped or prevented is increasing, new guidelines for the development of noncytotoxic drugs are required. To avoid duplication and to make the results obtained using these new agents comparable so that patients will gain the maximum benefit of efforts in this field, further extension of international coordination will be of utmost importance in the coming years.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a novel cytostatic agent that has shown interesting antitumor activity in patients with advanced breast cancer. Depending on variable patient characteristics and amount and type of prior therapy, as well as the applied dose and schedule of paclitaxel, response rates have varied from 13% to 62%. However, optimal dose and schedule are still unknown. We studied a high-dose (250 to 300 mg/m2) 3-hour paclitaxel infusion schedule in a poor prognostic group of breast cancer patients who progressed or relapsed while taking anthracyclines. This regimen was given every 3 weeks. Twenty-one of the 36 patients studied had increased liver enzymes and 18 had documented liver metastases. The objective response rate was only 6%, but response rate by disease site indicated that soft tissue lesions responded in 30% of cases. For a better comparison with other reported data a uniform definition of "anthracycline refractory" is needed. Neuropathy, which was found to be dose limiting, and arthralgia/myalgia syndrome were the most frequently occurring toxicities. Both severe myelosuppression (and infections) and severe diarrhea and mucositis were reported more frequently in patients with liver dysfunction. As higher peak levels, increased areas under the concentration time curves, and longer times during which plasma concentrations were above the threshold level of 0.1 mumol/L were found in patients with elevated liver enzymes, a correlation with the observed toxicities is assumed. Further pharmacodynamic studies in such patients receiving a 3-hour infusion seem warranted.