[Lung cancer in the elderly subject]. / Cancer bronchique du sujet âgé.

INTRODUCTION: In France, the average age for the diagnosis of bronchial carcinoma is 64. It is 76 in the population of over 70. In fact, its incidence increases with age linked intrinsic risk of developing a cancer and with general ageing of the population. Diagnosis tools are the same for elderlies than for younger patients, and positive diagnosis mainly depends on fibreoptic bronchoscopy, complications of which being comparable to those observed in younger patients. STATE OF THE ART: The assessment of dissemination has been modified in recent years by the availability of PET scanning which is increasingly becoming the examination of choice for preventing unnecessary surgical intervention, a fortiori in elderly subjects. Cerebral imaging by tomodensitometry and nuclear magnetic resonance should systematically be obtained before proposing chirurgical treatment. An assessment of the general state of health of the elderly subject is an essential step before the therapeutic decision is made. This depends on the concept of geriatric evaluation: Geriatric Multidimensional Assessment, and the Comprehensive Geriatric Assessment which concerns overall competence of the elderly. PERSPECTIVES: This is a global approach that allows precise definition and ranking of the patient's problems and their impact on daily life and social environment. Certain geriatric variables (IADL, BADL, MMSE, IMC etc) may be predictive of survival rates after chemotherapy or the incidence of complications following thoracic surgery. The main therapeutic principles for the management of bronchial carcinoma are applicable to the elderly subject; long term survival without relapse after surgical resection is independent of age. Whether the oncological strategy is curative or palliative, the elderly patient with bronchial carcinoma should receive supportive treatments. They should be integrated into a palliative programme if such is the case. In fact, age alone is not a factor that should detract from optimal oncological management. CONCLUSIONS: The development of an individual management programme for an elderly patient suffering from bronchial carcinoma should be based on the combination of oncological investigation and comprehensive geriatric assessment.

No age limit for radical radiotherapy in head and neck tumours.

The elderly are often treated less aggressively in an attempt to preserve their quality of life with regards to toxicity. However, there are few data regarding the acute and late toxicity of radiotherapy (RT) in elderly patients. From February 1980 to March 1995, 1589 patients with head and neck cancers who enrolled in EORTC trials received RT and were available for analysis on RT toxicity. Patients over 65 years of age were in excess of 20%. Data regarding age and acute objective mucosal reactions were available for 1307 patients and 1288 had toxicity > or = grade 1. Age and acute functional mucosal reactions were registered for 838 patients and 824 patients had toxicity > or = grade 1. Bodyweight alteration during treatment was available in 1252 patients; it increased in 153 patients and decreased in 1099 patients. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first- and second-line treatments. 749 patients were available for analysis of which 646 had late toxicity grade > or = 1. Survival and toxicity were examined in different age ranges from 50 to 75 years and over. There was no significant difference in survival between each age group. A trend test was performed to assess any correlation between age and the acute occurring toxicity. There was no significant difference in acute objective mucosal reactions (P = 0.1) and in weight loss > 10% (P = 0.441). In contrast, older patients had more severe (grade 3 and 4) functional acute toxicity (P < 0.001) than younger patients. We evaluated the probability of late toxicity occurrence in relation to time with the Kaplan-Meier method and the logrank test in each age group. Eighteen per cent of patients were free of late effects at 5 years, the logrank test showing no significant difference between ages (P = 0.84). In conclusion, chronological age is irrelevant for therapeutic decisions.

A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group.

This study tests the reliability and validity of the European Organization for Research and Treatment of Cancer (EORTC) head and neck cancer module (QLQ-H&N35) and version 3.0 of the EORTC Core Questionnaire (QLQ-C30) in 622 head and neck cancer patients from 12 countries. The patients completed the QLQ-C30, the QLQ-H&N35 and a debriefing questionnaire before antineoplastic treatment or at a follow-up. 232 patients receiving treatment completed a second questionnaire after treatment. Compliance was high and the questionnaire was well accepted by the patients. Multitrait scaling analysis confirmed the proposed scale structure of the QLQ-H&N35. The QLQ-H&N35 was responsive to differences between disease status, site and patients with different Karnofsky performance status, and to changes over time. The new physical functioning scale (with a four-point response format) of version 3.0 of the QLQ-C30 was shown to be more reliable than previous versions. Thus, the QLQ-H&N35, in conjunction with the QLQ-C30, appears to be reliable, valid and applicable to broad multicultural samples of head and neck cancer patients.

Age has no impact on acute and late toxicity of curative thoracic radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy is a treatment method frequently employed in the management of thoracic tumours. Although the highest incidence of these tumours is found in elderly people, tolerance to radiotherapy is not well documented in older age groups. Many physicians are tempted to alter the radiotherapy planning in a population with a supposed lower life expectancy in order to prevent acute reactions whereas late reactions are often ignored. The current study aimed to determine the influence of age on the frequency and severity of acute and late side-effects and also whether the prognosis of tumours sufficiently differed between ages to justify different attitudes towards their management. MATERIALS AND METHODS: Data from 1208 patients receiving chest irradiation and included in arms designed with RT of six EORTC randomized trials were evaluated. Data were extracted by a computer program elaborated for each study and were merged in a single database for analysis. Patients were split into six age ranges from 50 to 70 years and over. Survival and late toxicity were calculated with the Kaplan-Meier method and comparison between age groups was performed with the logrank test. The gamma-statistic test was used to test the impact of age on acute toxicity occurrence. RESULTS: Survival adjusted for the primary location of the tumour was comparable in each age group (P = 0.82). Data regarding age and acute toxicity were available for 1208 patients who experienced 640 grade > or =1 toxicities. The difference in distribution over age was not significant for acute nausea, dyspnea, oesophagitis, weakness and WHO performance status alteration. Weight loss was significantly different with regards to age with a trend toward increased weight loss in older age groups (P = 0.002). To minimize actuarial bias, only patients surviving more than 90 days were analyzed for late effect risks. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first and second line treatments. In such conditions, 1082 grade > or =1 late toxicities were recorded in 935 patients of 1106 available for analysis. The mean time to complication was 13 months and was similar in all age groups. Forty percent of patients were free of complication at 4 years, the logrank test showing no significant difference between age groups (P = 0.57). For grade >2 side-effects, the calculation did not show any difference between each age group (P = 0.1). A detailed analysis of late dyspnea and late weakness studied with the same method did not demonstrate any difference between age groups. Only grade >2 late oesophagitis demonstrated a significant trend to be more frequent in older patients (P = 0.01), but this difference disappeared after adjustment on study (P = 0.32). CONCLUSION: The absence of toxicity observed in the current study regardless of age reinforces the conviction that age per se is not a sufficient reason to exclude patients in good general condition with thoracic tumour from curative radiotherapy when medically indicated.

Quality control of radiotherapeutic treatment of medulloblastoma in a multicentric study: the contribution of radiotherapy technique to tumour relapse. The French Medulloblastoma Group.

Between 06.86 and 11.89, 88 medulloblastoma or primitive neuroectodermic tumour (PNET) localised in the posterior fossa have been included in the M7 multicentric protocol, 82 received the totality of the radiotherapy treatment and were evaluable for this study. Twenty-two of these 82 patients relapsed: their radiotherapy treatment is analysed in the present study. In 10 cases out of the 22 relapses treatment failure was probably due to a radiotherapeutic imperfection. This study confirms the necessity of a strict radiotherapy control, particularly in multicentric study.

Age is not a limiting factor for radical radiotherapy in pelvic malignancies.

BACKGROUND AND PURPOSE: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. MATERIAL AND METHODS: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. RESULTS: Survival was comparable in each age group for prostate (P = 0.18), uterus (0.41), anal canal cancer (P = 0.6) and slightly better for the younger group of rectum cancer (P = 0.04). A total of 1722 acute and 514 late grade > or = 1 were recorded. Acute nausea/ vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P = 0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P = 0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P = 0.79). For the grade > 2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P = 0.06) nor trend (P = 0.13) between age-groups. CONCLUSION: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies.

Carboplatin as radiosensitizer in non-small cell lung cancer after cisplatin containing chemotherapy. A phase I study of a groupe francais de pneumo-cancerologie (G.F.P.C.).

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca aklaloïd. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m2 per day, and increased to 15 mg/m2 per day and 20 mg/m2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62-66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40-45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time was 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m2 per day of either a bolus or continuous infusion.

Pharmacokinetics of high-dose methotrexate in adult osteogenic sarcoma.

The pharmacokinetics of 222 infusions of high-dose methotrexate (MTX) with leucovorin rescue were studied in 22 adults with osteosarcoma. To reduce the variability of plasma concentration, we individualized dose regimens using a Bayesian method to reach a concentration of 10(-3) M MTX at the end of an 8-h infusion. The mean concentration observed at the end of the infusion was 1016 +/- 143 mumol/l. The mean dose delivered was 13.2 +/- 2 g/m2. The clearance was 49.1 +/- 11.7 ml min-1 m-2. The decay of the plasma concentration of MTX after completion of the infusion followed a two-compartment model with a t1/2 alpha of 2.66 +/- 0.82 h and a t1/2 beta of 15.69 +/- 8.63 h. The volume of distribution was 0.32 +/- 0.08 l/kg. As compared with previously published data, the interindividual and intraindividual variations in the concentration at the end of the infusion were reduced, with values of 14% and 5.9%-21%, respectively, being obtained. Severe toxicities were avoided, and there were only 3 hematologic and 8 digestive grade 3 side effects and no grade 4 complication. The t1/2 alpha and the MTX plasma concentrations at 23 and 47 h were correlated with renal toxicity (P < 0.001). However, no correlation was found between the pharmacokinetic parameters and other signs of toxicity. There was no significant difference in pharmacokinetics between the toxic and nontoxic groups. In the same manner, the parameters of the group of patients sensitive to MTX were not statistically significant different from those of the group of nonsensitive patients.

Methotrexate-vindesine association in the treatment of head and neck cancer influence of vindesine on methotrexate's pharmacokinetic behavior.

Determination of methotrexate (MTX) kinetics after an IV bolus (50 mg/m2) allows prediction of the steady-state plasma level of this drug during a constant infusion. This prediction allows high-dose MTX (HD-MTX) therapy without major toxicity. Patients with head and neck carcinoma received HD-MTX and vindesine (VDS) infusions concomitantly. The therapeutic survey of these patients showed that the predicted plasma level of MTX was not achieved in the presence of VDS. Moreover, the computed dose of MTX had to be increased by a larger amount if the MTX plasma clearance after the identification IV push was low (less than 9 l/h). In the presence of VDS, the creatinine clearance is lower than when MTX is infused alone, and MTX renal elimination is identical (MTX or MTX + VDS infusions). Thus it seems that the decrease of the MTX plasma level during MTX-VDS infusion could be due to an increase of cellular incorporation.

Radiotherapy in the elderly.

Older patients with cancer are frequently victims of discriminatory treatment strategies according to parameters unrelated to the tumour itself. The general approach is influenced by the belief that good tolerance to radiotherapy might be compromised in older patients and that the course of cancer might be less aggressive in this age group. Substandard treatment is therefore often offered to older patients, although this attitude is supported neither by clinical nor by scientific evidence, but rather stems from a lack of specific knowledge of the actual cancer prognosis and the tolerance to radiotherapy in the elderly. In clinical practice advanced age may result in undertreatment, even though patients may have no other medical illness and no functional impairment. Some comorbid conditions which are more frequent in older patients may complicate the outcome of treatment. However, these impaired vital functions are not an intrinsic feature of the elderly. Overall, noncompliance in radiotherapy, related to comorbidity or technical condition, is rare. Short-term radiotherapy using a large daily fraction is often advocated in elderly patients; however, this should only be considered if a palliative treatment option has previously been selected due to the high risk of late side-effects. Acute side-effects often result in decreasing doses of radiotherapy. Data on acute tolerance of radiotherapy for different types of tumours did not demonstrate a radical difference in occurrence of toxicities. 'Reducing' radiotherapy is never a solution, unless the life expectancy of the patient is obviously so short that the tumour recurrence is unlikely to occur or at least to produce substantial morbidity before the patient has died from other causes.

Immunomodulation by NPT 15392 in cancer patients under chemotherapy.

A clinical trial of NPT 15392, a purine derivative, was run in ten head and neck cancer patients presenting signs of immunosuppression and undergoing repeated chemotherapy. A battery of ten tests was used to assess the immune status of the subjects. Those tests included skin tests, lymphocyte investigations (count, E-rosetting, membrane fluorescence and lymphoblastic transformation) and determination of serum levels of C'3 fraction of complement and IgA. The drug induced transitory, immune stimulation during or after treatment without any side effects. NPT 15392 seemed to selectively exert an action on T lymphocytes. Inasmuch as transitory, immune stimulation and secondary immune depression were noted after treatment, the therapeutic protocol for use of this drug should be reexamined.

[Colorectal cancer in Madagascar. A study of 81 cases diagnosed and treated at the Antananarivo General Hospital]. / Les Cancers colorectaux à Madagascar. Etude à partir de 81 cas diagnostiqués et traités à l'hôpital Général d'Antananarivo.

Colorectal adenocarcinoma are rare in Madagascar. Over a period of 8 years, such tumors were treated in the cancerology and surgery departments of Antananarivo. The low incidence and the relative young age at the time of diagnosis are comparable to observations made in other developing countries. Men represent 47 of the cases and women 34. On the average, patients were 52.3 years old (range: 23-78 years). The most frequent early symptoms are rectorrhagia (26 cases) for rectal cancer, abdominal pain (9 cases) and transit bowel disorders (9 cases) for colon cancer. Between the first symptom and diagnosis, the average delay is 8.5 months (range: 2 days-37 months). No risk factor was found. Thirteen patients did not receive any treatment, 8 were only submitted to radiotherapy and 60 were surgically treated with a curative intent in 26 cases, a palliative one in 32 cases and for diagnosis in 2 cases. Among the 63 tumors available for modified Dukes' classification of Astler-Coller, 9.5% are stage B1, 23.8% are stage B2, 11% are stage C1, 15.9% are stage C2 and 39.7% are stage D; there are no stage A. There is no epidemiological particularity for these cancers in Madagascar. The poor prognosis is probably mainly related to a lack of appropriate medical and surgical facilities.

[Management of breast cancer in Madagascar]. / Prise en charge du cancer du sein à Madagascar.

PURPOSE: Retrospective analysis of management and outcome of breast cancer in Madagascar. PATIENTS AND METHODS: From January 1996 to December 1998, 259 women with breast cancer were seen in the only department of oncology of the island, located in Antananarivo. It is equipped with a cobalt unit (unavailable in 1996). There was no uniform policy on surgery. Chemotherapy and hormonotherapy were not available for all patients. Reduced equipment enabled a minimal pre-therapeutic workshop. RESULTS: Mean age was 48.5 years. One hundred and fifty-six women were premenopausal. The majority (69%) lived less than 50 km from the department. Tumours were at an advanced stage in 67% of the cases; the mean delay for diagnosis was 9.4 months. Treatments were done with curative intent in 118 cases and with palliative intent in 64 cases. Partial surgery (89) was adequate in 40.5% of the cases; total mastectomy concerned 94 women. Axillary lymph node dissection was done in 94 cases and was positive in 76 cases. The number of involved nodes was noticed in 47 cases. Curative radiotherapy concerned 106 patients, 41 after total mastectomy and 44 after lumpectomy, and was exclusive in 21 cases. Palliative irradiation was done locally with hypofractionation for 35 patients. Chemotherapy was performed in 86 women. The 4-year survival of the 136 assessable patients was 73%. CONCLUSION: Improvement in breast cancer treatment outcome in Madagascar is the result of earlier diagnosis of the disease. Information and education of the population together with caregivers are necessary, because updating and improving technical equipment is not currently possible due to the economic problems that the country has to face.

[Cancer and the elderly. Management. Decision aspects]. / Cancer et sujets âgés. Prise en charge. Aspects décisionnels.

INTRODUCTION: Age is the major risk factor for the majority of patients with cancer. More than 50% of cancers occurs after the age of 60. Cancer in the elderly is therefore a public health issue at stake. However, in daily clinical practice the elderly presenting cancer are not listened to with great interest and treatment is often not proper or suboptimal. CURRENT KNOWLEDGE AND KEY POINTS: Diagnosis in the elderly is established at a more advanced stage of cancer than in younger people; diagnostic workup is reduced and suboptimal treatments are implemented. Therefore, barriers exist that prevent the elderly from accessing the healthcare system as easily as their younger counterpart. Misconceptions about cancer also lead them to delay their first visit. As well, although treatment with curative intent and without major side-effect is feasible, physicians have misconceptions regarding therapeutic possibilities. Due to the heterogeneity of the so-called "ageing population", difficulties are related to patients' selection. FUTURE PROSPECTS AND PROJECTS: Decision in oncology for the elderly must walk a fine line in attempting to deliver the best treatment under the best conditions. Age per se must not be the only criterion for medical decision. Providing accurate information adapted to the elderly, with large circulation among healthcare professionals, should lead to the same quality of care as that in young people. Comprehensive multimodal geriatric assessments should help to further differentiate patients who may benefit from curative treatment from those for whom only palliative treatment is necessary.

[Individual dose adjustment of high-dose methotrexate in clinical practice]. / Adaptation individuelle de posologie du méthotrexate à haute dose (MTX-HD) en pratique clinique courante.

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, the concept of high-dose methotrexate has been proposed. The use of rescue by folinic acid, as well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted us to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. Individual adaptation of posology, calculated using the test dose or according to population pharmacokinetic with a Bayesian method of parameter estimation (which allows us to adjust the dose of high-dose methotrexate during its infusion) permits control of inter and intra-individual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by high-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogeneous group of patients). Theoretical maximum concentration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum security for the patient with no serious side effects (no grade 4 toxicity according to WHO classification), while receiving an optimum dose of methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on average 65% more than the usual dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).

[Prediction of response to antineoplastic agents]. / Prévision de la réponse aux agents anticancéreux.

It now seems possible to predict response to anti-cancer drugs by means of several methods classified into three groups. Methods in the first group are aimed at determining the intracellular mechanisms required for the drugs to act on the tumoral cells; apart from hormone receptor assays, few of these have practical applications. Methods in the second group are concerned with the action of cytostatic drugs on malignant cells; clonogenic cultures and human tumour xenografts in mice are already routinely used. Finally, methods to evaluate the pharmacokinetics of anticancer drugs are being developed. These three groups of methods can be used in the pre-clinical screening of these drugs or at the clinical trial phase to predict individual responses to chemotherapy.

[Concomitant radiotherapy-chemotherapy for unresectable cancers of the head and neck: a retrospective analysis of 130 patients]. / Radiothérapie-chimiothérapie concomitante des cancers non opérables de la tête et du cou. Etude rétrospective sur 130 patients.

OBJECTIVES: We analyzed retrospectively the files of 130 patients with unresectable cancer of the head and neck who were given concomitant radiotherapy-chemotherapy between January 1993 and February 2000. PATIENTS AND METHODS: The series included 41 patients with grade III cancer, 64 grade IVA, and 25 grade IVB. Treatment combined radiotherapy (70.2 Gy centered on the tumor with 50.4 Gy on the lymph nodes) and chemotherapy using three cycles of cisplatinium combined with 5-fluorouracil in continuous infusion for 120 hr. RESULTS: Local control was achieved in 51% of the patients at two years and 48% at five years. Overall survival was 45% at two years and 33% at five years, all grades included. CONCLUSION: Univariate analysis of prognostic factors points out the importance of the nutritional status before and during treatment.