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Biomedical subjects

H Pinedo

Publications and source records attributed to H Pinedo.

7 recordsLinked to original sources

Essential drugs for cancer therapy: a World Health Organization consultation.

The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible.

Antineoplastic Agents↗

Future perspectives.

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Antineoplastic Agents, Phytogenic↗

TCNU (LS 2667), a new active drug in the treatment of advanced colorectal cancer. EORTC Early Clinical Trials Group.

Fifty-seven patients with advanced measurable or evaluable colorectal cancer not previously treated with chemotherapy and tumor manifestations from colorectal cancer were treated with tauromustine (TCNU), a new nitrosourea with a therapeutic index against murine tumors better to or equal to that of the established nitrosoureas. The dose was 130 mg/m2 orally q 5 weeks. There were one CR and seven PR, for an overall response rate of 14%. Responding sites included the liver (one CR and two PR), lung (four PR) and lymph nodes (two PR). The median duration of response was 33+ weeks (21+ to 34 weeks). The main dose limiting toxicity was myelosuppression which seemed to be cumulative. Subjectively, the drug was well tolerated although most patients experienced nausea and vomiting for some hours. It is concluded that TCNU is a well tolerated compound with limited, but definite antitumor activity against colorectal cancer and that further studies in this disease could be of interest.

Adenocarcinoma↗

Phase II study of iproplatin in advanced ovarian carcinoma.

Iproplatin (cis-dichloro-trans dihydroxy-bis-isopropyl-amine platinum [IV]; CHIP) was administered intravenously (IV) at monthly intervals at doses of 300 mg/m2 and 240 mg/m2 to ten previously untreated and 97 previously treated patients with advanced ovarian carcinoma. The overall response rate was 78% among patients with no prior chemotherapy, 42% among patients with prior chemotherapy not including cisplatin, and 22% among patients with prior chemotherapy including cisplatin. Overall response rates to iproplatin were 6.4% and 54% in patients with/without clinical evidence of tumor resistance to cisplatin. Thrombocytopenia was the dose-limiting toxicity, median time to nadir and to recovery being 2 and 4 weeks, respectively. Patients who had received prior chemotherapy regimens for greater than 1 year showed a 10% greater reduction in platelet count (mean platelet nadir +/- SD, 57.5 +/- 49.96 X 10(3)/microL) and a higher incidence of grade 3 to 4 thrombocytopenia after the first cycle than patients who had received prior chemotherapy regimens for less than 1 year (94.7 +/- 65.99 X 10(3)/microL) Moderate to severe vomiting and diarrhea occurred in 84% and 16% of patients pretreated with chemotherapy. Neuropathy (6%) was reported only in patients with prior cisplatin treatment. Mild and reversible renal toxicity was observed in 6% of cases. Iproplatin is an active drug in ovarian cancer; the results achieved in patients previously treated with cisplatin strongly suggest that the two drugs are cross-resistant.

Antineoplastic Agents↗

Phase II study of 5'-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma.

Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily X 5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts less than 1.5 X 10(9)/l leukocytes or 50 X 10(9)/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.

Drug Evaluation↗

Phase II trial of diaziquone (AZQ) in advanced malignant melanoma.

Forty-two evaluable patients with malignant melanoma received AZQ 27 mg/m2 i.v. every 4 weeks. In 5 patients with poor marrow reserve this dose was reduced to 20 mg/m2. Doses were rapidly escalated when no significant myelosuppression was encountered in previous courses. Twenty-five patients had received no prior chemotherapy. A single partial response was obtained for 3 months. Inconsistent myelosuppression was the main toxic effect in this trial. The median WBC and platelet nadirs were 3200/mm3 (900-19,500) and 105,000/mm3 (33,000-530,000) respectively. In 2 patients leukopenia was complicated by a transient episode of infection. One-third of the patients did not experience significant myelosuppression. Non-hematologic adverse reactions were generally mild to moderate and consisted of nausea and vomiting in 26 patients and alopecia in 1. It is concluded that at this dose schedule AZQ is ineffective against malignant melanoma.

Adult↗