Peripheral neuropathy is a common manifestation of chemotherapeutic agents. Most drugs produce a distal axonal degeneration and long axons are predominantly affected, giving a clinical picture characterized by a symmetrical sensory neuropathy. The toxicity of therapeutic agents to the peripheral nervous system particularly includes those used in cancer-chemotherapy (cisplatin, vinca alkaloids), but antimicrobial agents such as isoniazide or nitrofurantoin and vitamin abuse (pyridoxine) are also discussed.

With cancer patients, the venous access remains a major problem. It causes phlebitis, venous sclerosis, skin necrosis and sepsis. Its maintenance implies careful nursing and a great dependence for the patient. Arterio-venous fistulas have been abandoned and replaced by Hickman-type subcutaneous indwelling catheters. These have a complication rate, mainly infectious, of about 0.4/100 days. The development of totally implanted catheters diminishes even more this rate and improves the patient's comfort. In this article we report the experience gained from 100 cancer patients equipped with 107 catheters. 31 complications occurred over a total time of 15,421 days, this averages a rate of 0.2 complications/100 days. The respectively rate of thrombosis and infections are of 0.02/100 days each. In 61% of the cases the whole system was functional after management of the complication. This results confirm the excellent tolerance of the system, its minimal rate of complication and its great possibility of reutilization.

Over 8 1/2 years, we observed 27 patients with drug-induced respiratory disease (DIRD). The inducer drugs were mainly those used in cardiology (9 patients, of whom 8 had amiodarone pneumonitis), in oncology (8 patients), in rheumatology (4 patients; 3 from d-penicillamine and 1 from gold), and in neurology (4 cases from ergoline derivatives). The main pattern of DIRD was a diffuse interstitial lung disease having either a rapid, a slowly progressive or a chronic course. Only the two former patterns offered clearing following withdrawal of the drug. Severe bronchiolitis obliterans from d-penicillamine (2 cases) and pulmonary eosinophilia (2 cases) was also observed. The onset of DIRD occurred earlier, i.e. following shorter periods of drug administration (months), in the acute interstitial lung disease variant, while it occurred after years of drug exposure in subacute and chronic forms. In contrast to other reports, bronchoalveolar lavage lymphocytosis was not a prominent feature in amiodarone pneumonitis. The outcome was favourable in 16 patients; deaths was encountered during the florid phase of DIRD in 3; incapacitating sequelae were noted in 6 patients, leading to subsequent death in 2; the underlying disease accounted for 7 additional deaths. Therefore, DIRD are relatively common, develop often in patients with severe underlying conditions, and interstitial pneumonitis is their pattern of predilection. Amiodarone emerges as a common inducer, and accounted for more cases than all chemotherapeutic agents grouped together in our series.

This article details the pernicious odontostomatological effects provoked by antitumorous and immunosuppressive medication. The role of the dentist as a member of the chemotherapeutic team is highlighted as well.

Ninety-two patients with carcinoma of the esophagus were treated with pre-operative chemotherapy (2 courses) before undergoing surgery. Chemotherapy and/or radiation were carried out after surgery depending on the tumor response to chemotherapy and extent of the tumor found at surgery. Tumor response before surgery (according to OMS criteria) was determined in 84 patients. Forty-four percent of patients showed a tumor regression of over 50%. Curative surgery was more frequently performed in patients with good tumor regression (greater than 50%) than in patients with less satisfactory tumor regression (less than 50%) (76 versus 57.5% respectively) (P = 0.08). Patients who underwent curative surgery had a lower pathologic staging when tumor regression was over 50%. However, the number of patients is too limited for any definite conclusions to be made. Survival rate at 3 years was similar in both groups of patients with curative surgery. Survival was not influenced by the extent of tumor regression before surgery. This study also suggests that the pre-operative chemotherapy did not increase the survival rate of patients who underwent curative surgery. Therefore it does not seem advisable to undertake a phase III randomized study on pre-operative chemotherapy patients.

Chemotherapy of metastatic breast cancer induces temporary tumor responses, without any incidence on vital prognosis. New drugs are sometimes less toxic than previous but are not more efficient. Such findings are observed with other schedules of chemotherapy. It is necessary to adapt treatment to expected goal: optimal efficacy or minimal toxicity.

Fifty-eight patients with colorectal liver metastases were treated by intra-arterial hepatic chemotherapy (IAHC) containing 5 FU (n = 42) or FUDR (n = 16). Twenty-three patients (39.6 p. 100) complained of abdominal pain. In three of these patients, the course was complicated by digestive hemorrhage. Endoscopic explorations and angioscintigraphy were normal in 4, showed oesophagitis in 3, superficial gastritis or duodenitis in 8 (34.7 p. 100) and gastric (2) or duodenal ulceration (6) in 8 (34.7 p. 100). The duodenal ulceration was extensive and considered to be cause of hemorrhage in two cases. Duodenal perforation due to the catheter was discovered in two other cases, one of which was secondary to tumoral extension revealed by forceps biopsy. This patient died 3 months later. Surgical treatment was mandatory in the other case due to digestive hemorrhage but did not prevent death. Angioscintigraphy performed in 15 patients with gastroduodenal inflammation or ulceration was normal in 7 patients, revealed arterial thrombosis in 5 and an extra-hepatic perfusion in the gastroduodenal area in 3 : this was related to a small pyloric artery which was occluded secondarily. IAHC was continued there after. This experience underlines the importance of exploring patients with digestive symptoms during IAHC so that it may be temporarily discontinued while an inadequately positioned infusion catheter may be corrected should gastroduodenal ulceration occur.

Intra-arterial hepatic chemotherapy is effective in the treatment of colorectal or endocrine carcinomas liver metastasis. However it is potentially toxic for the healthy liver. To check this, we studied non tumoral liver specimens in 14 patients treated by intra-arterial chemotherapy with 5 fluorouracil, 5 fluoro-2 deoxyuridine and an association of 5 fluorouracil and streptozotocin. The main hepatic lesions observed were: sclerosing cholangitis, central vein (dilatation and fibrosis) and moderate hepatocellular necrosis or cholestasis in the centrolobular area. Thus intra-arterial hepatic chemotherapy has important toxic effects on healthy liver, even if clinical and biological liver disturbances are minimal in most cases. Caution must be exercised in using this method.

Fotemustine (S 10036) is a new nitrosourea compound whose antitumoral activity has been demonstrated, particularly in disseminated malignant melanoma. Pharmacokinetic parameters of this drug were investigated during phase II clinical trials and compared according to tumor type. Twenty-six patients entered the study and received an induction treatment (weekly 100 mg/sq.m of fotemustine in 250 ml of 5% glucose in water over a one-hour IV infusion for 3 consecutive weeks) followed by a 4-week rest period. A maintenance therapy (100 mg/sq.m every three weeks) was proposed in stabilized or responsive patients. Plasmatic assay of fotemustine was carried out by HPLC. Seventy-one cycles were analyzed. A short half-life and a large intra and inter-individual variability of all kinetic parameters (especially plasmatic clearance) was found independent of tumour type. The study of patient's clinical behaviour was shown to be related to the clearance value obtained during the first treatment cycle which seems to predict the clinical response in the case of malignant melanoma. This finding needs to be confirmed in a larger number of patients and in other tumor localizations.