Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a haematopoietic growth factor with a wide variety of applications in the clinic. In early phase I studies the continuous intravenous (c.i.) route of administration was often used. Later it was shown that subcutaneous (s.c.) administration was also effective. The optimal route of administration remains, however, poorly defined, and no studies have made a direct comparison between these two routes of administration. We treated patients with advanced breast cancer with moderately high-dose doxorubicin and cylophosphamide and GM-CSF. The first 14 patients received GM-CSF by c.i, while subsequently 47 patients received it s.c. Comparison between the two groups showed that c.i. GM-CSF was more toxic in several respects. There was a higher need for erythrocyte and platelet transfusions and a significant deterioration in the performance status. This study indicates that subcutaneous GM-CSF is the preferred route of administration. Randomised trials are, however, needed to confirm these conclusions.     

Induction chemotherapy with cisplatin and continuous infusion 5-fluorouracil in locally far-advanced head and neck cancer

Induction combination chemotherapy with cisplatin, 100 mg/m2 i.v. day 1, and 5-fluorouracil, 1,000 mg/m2/24-h infusion days 1-4, was applied in 76 patients with locally far advanced squamous-cell cancer of the head and neck. The treatment program consisted of 3 cycles of chemotherapy, followed by local radiotherapy and/or surgery. Hematologic side effects were leukocytopenia (50%) and thrombocytopenia (35%). Other side effects included renal toxicity (23%), nausea and/or vomiting (86%), alopecia (18%), and phlebitis (45%). Thirteen patients (17%) achieved a complete remission and 37 patients (49%) a partial remission. Median progression-free and overall survival were 8 and 11 months, respectively. Only patients achieving a complete remission had a better prognosis. Although induction chemotherapy may facilitate further local treatment in about half of the patients, on the basis of presently available data, this procedure should not be routinely applied with the aim of better survival.     

Comparison of two different high doses of metoclopramide in the prevention of chemotherapy-induced emesis

A randomized double-blind study was conducted to compare the anti-emetic efficacy of 1 mg/kg vs 2 mg/kg metoclopramide, administered 5 times over a period of 8.5 h in 50 cancer patients treated with platinum-containing regimens (cisplatin, ethylenediamine platinum II malonate or spiroplatin). Twenty-six patients were treated with combination chemotherapy, mainly consisting of cisplatin and 5-fluorouracil. No statistically significant differences were observed with respect to the protection against nausea and vomiting between the two dose levels of metoclopramide. However, in the group of patients who received a high dosage of cisplatin (70-100 mg/m2), or ethylenediamine platinum II malonate (800-900 mg/m2), there was a significant difference in nausea and vomiting between patients who had and those who had not received prior chemotherapy, most probably due to anticipation. No difference in the severity of the side effects was observed with the 2 metoclopramide dose levels. Considerable interpatient variation was present in serum metoclopramide levels. No clear correlation was observed between serum metoclopramide levels and prevention of platinum-induced emesis. We conclude that 1 mg/kg of metoclopramide is just as effective as 2 mg/kg as an anti-emetic agent in patients receiving platinum-based chemotherapy, and that metoclopramide serum levels are not related to the anti-emetic effect.     

What did the doctor say--what did the patient hear? Operational knowledge in clinical communication

OBJECTIVES: We aim to introduce Piaget's concept of 'operational knowledge' from the cognitive theory of learning--as a contribution to the broader understanding of clinical interaction. METHOD: Our study involves a theoretical presentation of different kinds and levels of human understanding, illustrated by a case story in which the difference between operational and figurative knowledge was demonstrated. This study used the case story of a male patient aged 80, who was suffering from ulcerative colitis. We appealed to the reader's perceived relevance of these perspectives, in order to understand what was going on between doctor and patient. RESULTS: The case story demonstrates the phenomenon of operational knowledge in the patient, the close links between communicative action and cognitive understanding, and the importance for the doctor of reflecting upon this level of interaction. CONCLUSION: According to the patient-centred clinical method, the doctor should explore the social and emotional context of the patient in order to understand the meaning of the illness. We suggest that a cognitive dimension should also be added, and that the concept of 'operational knowledge' might be useful for such investigations.      

Mucocutaneous side effects of Brequinar sodium. A new inhibitor of pyrimidine de novo biosynthesis

Brequinar sodium (NSC 368390; DUP 785) is a new inhibitor of pyrimidine de novo biosynthesis which has completed Phase I clinical trials within the framework of the Early Clinical Trials Group of the European Organization for Research and Treatment of Cancer (EORTC). The main side effects of this compound are myelosuppression, nausea and vomiting, stomatitis and/or mucositis, and skin rash. In this report, the authors describe the pattern of mucocutaneous side effects of Brequinar sodium in patients who received the drug by four different schedules: (1) short-term intravenous (IV) infusion every 3 weeks; (2) weekly; (3) twice weekly; and (4) five times daily every 4 weeks. Mucocutaneous toxicities of Brequinar sodium included mainly cytotoxic reactions (stomatitis and/or mucositis and skin rash). However, rare episodes of local reactions (phlebitis at the site of injection), photosensitivity reactions (to sun light), angioneurotic edema, and localized secondary hyperpigmentation of the inflamed skin also occurred. Stomatitis and/or mucositis appeared to be dose-dependent and schedule-dependent. The skin rash consisted of a drug-induced toxic dermatitis which occurred mostly at the highest dose levels. Initial recommendations for the management of mucocutaneous toxicities of Brequinar sodium during Phase II trials are discussed.     

Work in progress: radioprotection of human breast cancer cells by elevation of intracellular cyclic AMP

MCF-7 human breast cancer cells that were treated for one hour prior to X irradiation with the cyclic AMP-inducing agent 1-methyl-3-isobutylxanthine displayed a slight but significant increase in surviving fraction over untreated controls at each radiation dose level. This was accompanied by a two-fold increase in the level of intracellular cyclic AMP.