In vitro interactions of TNO6 with human plasma.

The ability of TNO6 to react with human plasma was investigated by in vitro incubation of plasma or plasma fractions with injectable TNO6. HPLC, ultrafiltration and flameless atomic absorption spectrophotometry were used to separate the platinum-containing chemical species and to measure the platinum content. The initial concentration of TNO6 in plasma declines very rapidly. The kinetics of the loss of initial TNO6 is very different from that of cisplatin loss. Most of the TNO6 is bound more quickly to proteins, while a little is transformed to less reactive or nonreactive platinum species. The level of final nonreactive platinum species depends on the particular plasma concerned. In addition, the reactivity of TNO6 towards proteins is very sensitive to Cl- concentration. The usefulness of HPLC for the study of TNO6 kinetics is demonstrated.

Platinum concentration in human tumors of head and neck, uterine cervix, and breast following treatment with cisplatin.

Intratumoral platinum concentrations were measured in three tumor sites (head and neck, uterine cervix, and breast) 48 h after cisplatin administration according to the same protocol. The platinum levels were in the same order of magnitude in all tumors, but the concentration in breast tumors was found to be higher than that in tumors of the head and neck and of the uterine cervix.

Sequential measurement of intratumoral platinum concentration in cervix uterine tumors after cis-dichlorodiammineplatinum (CDDP) administration.

Intratumoral (cervix uterine tumors) distribution of platinum was studied in ten patients after IV administration of CDDP. Sequential tumoral measurement of platinum was carried out 4, 24, and 48 h after the IV infusion. Platinum concentration in the tumor samples ranged from 0 to 29,5 ng/mg tissue. For all patients, there was no definite evolution of the tumoral concentration with time and there was no good relation for the same patient between the platinum concentration in three successive biopsies. These results involve uncertainty in studies attempting to relate CDDP tumor levels (measured in one biopsy) and tumor response to chemotherapy.

Evaluation of the bioequivalence of tablet and capsule formulations of granisetron in patients undergoing cytotoxic chemotherapy for malignant disease.

Granisetron is a novel, highly specific 5-hydroxytryptamine receptor antagonist given prophylactically to patients undergoing chemotherapy. An open, randomized, crossover trial was performed with 37 patients (24 females and 13 males) undergoing cytotoxic chemotherapy for malignant disease to compare an oral tablet (1-mg tablet given twice daily) with a clinical-trial capsule (1-mg capsule given twice daily). Complete pharmacokinetic data were determined for 24 patients (14 females and 10 males). The concentration of granisetron in plasma was measured by HPLC; the limit of quantitation was 0.2 ng/mL. The bioavailability evaluation was based mainly on the area under the curve (AUC) (mean values: 52.1 ng.h/mL for the capsule and 54.2 ng.h/mL for the tablet) and the maximum concentration (Cmax) (mean values: 7.42 ng/mL for the capsule and 8.18 ng/mL for the tablet) measured at the steady state after 7 days of continuous therapy. Wide interpatient variability in plasma granisetron levels after oral administration was observed. The 90% standard confidence interval for the geometric mean ratio overlapped the critical range, 0.8-1.25. Point estimates for AUC and Cmax based on two one-sided t tests and log-transformed data showed that the upper limit of the confidence interval was not within 20% of the mean for the capsule; the corresponding power analysis values for AUC and Cmax were 0.89 and 0.81, respectively. Despite bioequivalence not being proven, any differences that exist between the two formulations are likely to be small. There was no difference in efficacy or safety between the two formulations assessed.

Significance of PSA and PAP in patients with or without prostatic cancer.

Coupled prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measurements (using the radioimmunoassay method) were carried out on 220 controls, 33 patients with prostatic hyperplasia, and 71 with carcinoma. The mean PSA value was 3.70 +/- 3.31 ng in the controls. A level of 10 ng was adopted as the upper limit of normal. Four of the eight cases of prostatic hyperplasia with a high PSA level (between 10 and 25 ng) underwent surgery. Histological tests confirmed benign hyperplasia. In the localized cancers, the PSA level was normal. In the metastatic cancers, PSA proved to be more sensitive than PAP. Thus, PSA is of little use in the early diagnosis of cancer; its systematic measurement as a means of cancer screening for the general public may even be misleading.

Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial.

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

[Registry of cancers of the upper respiratory and digestive tract at the Northern and Pas-de-Calais departments from 1984 to 1986]. / Registre des cancers des voies aérodigestives supérieures des départements du Nord et du Pas-de-Calais 1984-1986.

Northern France is known to have the highest mortality rate for cancers of the upper aerodigestive tract (UADT); a UADT cancer registry was therefore set up in this region in January 1984. Three years of meticulous registration provided some significant information. The incidence of UADT cancer was alarming: 4538 UADT cancers in 4403 patients. Most of the patients were males (93.5%). The annual average incidence was 74 per 100,000 males as against 4.8 per 100,000 females. Comparisons with adjusted rates for the European population (91.3 per 100,000 males, 4.8 per 100,000 females) and the world population (68.3 per 100,000 males and 3.6 per 100,000 females) further justified this conclusion. The accuracy of histopathological diagnosis was high (precise diagnosis in 99.2% of the patients). Squamous cell cancers were the commonest form of tumours (97.8%). Oropharynx (27%), larynx (24%) and the hypopharynx (18%) were the most frequent localizations.

Comparison of platinum concentrations in human head and neck tumours following administration of carboplatin, iproplatin or cisplatin.

Tumour tissue levels of platinum were determined in patients with head and neck tumours receiving carboplatin (11 patients, 400 mg/m2) and iproplatin (5 patients, 360 mg/m2). The platinum concentrations ranged from 1.1 +/- 0.4 ng Pt/mg tissue (iproplatin administration) to 1.4 +/- 0.3 ng Pt/mg tissue (carboplatin administration). These results were compared with published platinum levels after cisplatin administration. Although the administered dose of carboplatin (1.08 mmol/m2) and iproplatin (0.86 mmol/m2) was higher than the cisplatin one (0.33 mmol/m2), no significant statistical differences were observed in the resulting platinum tissue levels. The constancy of tumour platinum level after treatment with different platinum complexes could be explained, at least for carboplatin and cisplatin, by both the tumour diffusion properties and the reactivity of the drugs.

[Continuous Holter cardiac monitoring and chemotherapy by combination with platinum and fluoro-uracil]. / Enregistrement cardiaque continu par Holter et chimiothérapie par une association de platine et de fluoro-uracile.

Thirty-three male patients (pts) were given cisplatin and fluoro-uracil (1 g/m2/d) in IV continuous infusion over 96 h, for the primary or palliative treatment of locally advanced head and neck cancer. The mean age was 52 +/- 7 years (range: 37-65). Patients underwent continuous ECG monitoring and were monitored for 22.4 +/- 1.5 h before FU infusion, 91.9 +/- 7.3 h during FU infusion and 18.5 +/- 2 h after 5FU infusion. Patients were given one cycle of chemotherapy (32 pts), two (25 pts) or three consecutive cycles (20 pts). Seventeen pts (53%) had supraventricular arrythmia, 15 pts (47%) had ventricular arrythmia and 10 pts (31%) had ST segment deviation. The ECG abnormalities were more frequent during the first cycle of chemotherapy. No previous clinical or ECG parameter was associated to ECG changes. Platin-induced hypomagnesemia and hypokaliemia probably increase incidence of cardiac abnormalities, during and after FU infusion.

Uptake of platinum compounds in human tumors. In vitro study.

The kinetics of intratumoral uptake of cisplatin, carboplatin (CBDCA) and TNO-6 were studied in vitro in fragments of tumors of the head and neck maintained in culture medium under conditions simulating therapeutic conditions of chemo-embolization. Cisplatin and TNO-6 are more rapidly taken up than CBDCA (carboplatin). With each of these compounds, after 24 hours a fraction of the platinum taken up is not irreversibly bound to the tissue. The rate of uptake and the proportion of platinum irreversibly bound depends a great deal on the tumor under study. The characteristics of the diffusion indicate that TNO-6 is better used with chemo-embolization than with systemic injection. The opposite finding is seen with carboplatin. Cisplatin appears to to be about equally well-suited for either method of injection.

[The use of the pectoralis major myocutaneous flap in cervicofacial and particularly buccopharyngeal, surgery. Apropos of 42 cases]. / L'apport du lambeau musculo-cutané de grand pectoral en chirurgie cervico-faciale et notamment bucco-pharyngée. A propos de 42 cas.

During the last two years, we have used a pectoralis major myocutaneous flap in 42 cases (28 after radiotherapy). The immediate post-operative periods were very simple and the flap reliability was remarkable: only three partial necrosis and no total necrosis were observed. This technique seems to be an important contribution in the field of buccopharyngeal surgery, especially in the case of extensive tumors involving the tongue. In that case, initial radiotherapy followed by extensive surgery with myocutaneous flap reconstruction seems to be the best therapeutic strategy. It is the authors' feelings that local control will probably be better but long term results will be still poor. Effectively, in case of extended tumors general prognosis has to be taken in account as well as local prognosis.

[Nasopharyngeal epitheliomas: experience of the Regional Cancer Control Center in Lille (79 cases 1970-1982)]. / Les épitheliomas nasopharyngés: expérience du Centre Régional de Lutte contre le Cancer de Lille (79 cas de 1970 à 1982).

From 1970 to 1982, 79 cases of nasopharyngeal carcinomas were treated at the Regional Cancer Center of Lille (France). At the term of the study, it appears that patients of Central Europe origin have a rather high risk of NPC (17% of cases, that ethnic population representing about 8% of all superior aerodigestive tract carcinomas). The classical differences between well and undifferentiated tumors are founded, the first presenting local spread the other general involvement.

Lymphocytes T and pharmacokinetics after a single oral dose of levamisole in healthy and cancer subjects.

Levamisole, an anthelmintic drug with immunopotentiating activity, is shown to have variable effects on cell-mediated immunity. We have studied the effect of a single oral dose (2.5 mg/kg or 5 mg/kg) on early and spontaneous E rosettes percentages in healthy and cancer patients. Pharmacokinetic study of this compound was conducted in parallel. The results indicated that single administration of levamisole (2.5 mg/kg) in healthy men can promote an increase of early E rosettes with mean peak plasma level of 0.8 micrograms. ml-1. On the other hand, there was no change in the proportion of early E rosettes in cancer patients and in the proportion of spontaneous E rosettes in healthy and cancer subjects.

[Hypopharyngeal cancer in the Northern region and Pas-de-Calais. Epidemiological factors]. / Cancers de l'hypopharynx dans la région Nord et Pas-de-Calais. Facteurs épidémiologiques.

Authors report results of two epidemiological studies concerning hypopharynx cancer. The first one is a part of the head and neck cancer registry of Northern France from 1984 to 1987. Hypopharynx tumors represent 18% of the 6019 registered tumors, 99% are squamous cell carcinoma; the annual european standardized incidence rate is 17.0 per 100,000 males and 0.5 per 100,000 females. The second one is a prospective study of 339 hypopharynx cancer patients: 1 out of 3 lives alone and 1 out 3 works at the moment of diagnosis. The average daily tobacco and alcohol consumption are 24 g and 128 g respectively, without any difference regarding professional exposures.

[Occult cancer of the breast]. / Les cancers infracliniques du sein.

21 cases of occult breast cancer were reviewed retrospectively. The patients were followed up from 1 to 9 years. Only one of these patients had partial axillary nodal disease and none had recurrence of mammary neoplastic disease. Thus, the prognosis of occult breast cancer is much better than that of clinical breast cancer and we think that all possible efforts must be made it order to detect breast cancer earlier. Mammography seems to be the best form of screening and in our opinion in every suspect disease surgical exploration must be performed.

[Registry of cancers of the upper aero-digestive tract in departments of the North and Pas-de-Calais. Report for the year 1984]. / Registre des cancers des voies aéro-digestives supérieures des départements du Nord et du Pas-de-Calais. Bilan de l'année 1984.

The authors give the results of the head and neck carcinoma registry in the Northern France at the end of the first registration year. This registration was easily carried out with a pathologic diagnosis known in 99% cases. The carcinoma incidence is rather high in this French country: 1 636 new cases, i.e. an incidence about 79.5/100 000 males. The most frequent are buccopharyngeal carcinoma. It seems to exist some differences between different Northern districts which shows the necessity of epidemiologic studies and of such a registry.

[Carcinomas of the upper aerodigestive tract before age 40 (excluding children). Apropos of 100 cases]. / Les carcinomes des voies aérodigestives supérieures avant 40 ans (enfants exclus). A propos de 100 cas.

A series of 100 young adults with carcinoma of upper respiratory and digestive tracts; and examined successively, is reviewed. As in older adults, the oropharynx was the most frequent localization with, in contrast, fewer endolaryngeal tumors and more rhinopharyngeal cancers. Progression appeared to be more rapid in young adults and alcohol and smoking a more important factor than in the older age group. Overall prognosis in the older age group. Overall prognosis seemed somewhat better for these younger patients. Epidemiologic surveys would appear to be essential.

[Metastasis of visceral tumors in intracranial tumors. Apropos of a metastasis of a lung cancer in an intracranial meningioma]. / Les métastases des cancers viscéraux dans les tumeurs intracrâniennes. A propos d'une métastase d'une cancer pulmonaire dans un méningiome intracrânien.

In a 52 years old man a backward epilepsy revealed a left fronto parietal tumor. The histopathological study shows that it is a meningial tumor composed around by meningocytic proliferation with a metastasis of lung cancer in the middle. This fact was proved only two months after neurosurgical intervention. Thirty three cases of cancer with metastasis in an intracranial primitive tumor have been collected in the literature. The authors study the clinical aspects and etiopathogenic hypothesis of this surprising anatomopathological fact.

[Cervical adenopathies of unknown primary site. Apropos of 190 cases]. / Les adénopathies cervicales sans porte d'entrée. A propos de 190 cas.

From 1974 to 1983 a total of 190 patients with metastatic cervical adenopathy from an undetected epidermoid cancer were treated, this group representing 3% of total cervicofacial tumors seen. In half the cases the lymph node had evolved over more than 3 months and measured 6 cm or more. Prognosis was poor (27% survival at 3 years and 19% at 5 years). The presumed primary tumor was detected in 16% of cases and 27% of patients developed distant metastases, whereas the 86 patients treated by neck dissection and irradiation showed cervical evolution in only 23% of cases. The therapy proposed includes total radical neck dissection followed by pharyngeal and bilateral cervical irradiation, the value of chemotherapy remaining to be determined during controlled trials.

[Different modalities of the radiosurgical combination in the treatment of tumors of lateral buccopharyngeal junction]. / Les différentes modalités d'association radio-chirurgicale dans le traitement des tumerus de la jonction bucco-pharyngée latérale.

Results are presented of combined transmaxillary buccopharyngectomy-radiotherapy treatment of 290 tumors of lateral buccopharyngeal junction. Post-therapeutic course was uncomplicated but 8 postoperative deaths are reported. Secondary extension of tumor was noted in 109 patients and another cancer in 64. Actuarial survival at 3 years was 54%, at 5 years 39% and at 10 years 17%. Lingual and muscle extensions were the most difficult to control and first intention excision is therefore performed when bone invasion has occurred. In contrast, total dose radiotherapy should probably precede surgery for forms with lingual and/or muscle extension.