Impaired Geriatric 8 Score is Associated with Worse Survival after Radiotherapy in Older Patients with Cancer.

AIMS: To investigate whether the Geriatric 8 (G8) score and the Timed Get Up and Go Test (TGUGT), together with clinical and demographic patient characteristics, are associated with survival and late toxicity after (chemo)radiation therapy, administered with curative intent in older patients with cancer. MATERIALS AND METHODS: Four hundred and two patients aged ≥65 years (median age 72 years, range 65-96 years), diagnosed with either breast, non-small cell lung, prostate, head and neck, rectal or oesophageal cancer, and referred for curative (chemo)radiation therapy, took part in a multicentre prospective cohort study in eight radiotherapy centres in the Netherlands. The G8 and TGUGT scores were assessed before starting treatment. Other potential predictors and late toxicity were also recorded. Survival status and date of death, if applicable, were ascertained at the Dutch national death registry. RESULTS: After 2.5 years, the overall survival was 83%. Survival was 87% for patients with high G8 scores and 55% for patients with low G8 scores (Log-rank P value < 0.0001). Survival was 77% for patients with good TGUGT results and 50% for patients with poor TGUGT results (Log-rank P value < 0.001). In multivariable analysis, in addition to age and type of primary tumour, the association of the G8 score with overall survival remained, with a hazard ratio of 2.1 (95% confidence interval 1.2-3.8) for low versus high scores. CONCLUSIONS: G8 was associated with overall survival in older patients with cancer irradiated with curative intent. This association was independent of the predictive value of age and primary tumour.

Irinotecan and cisplatin with concurrent thoracic radiotherapy in a once-every-three-weeks schedule in patients with limited-disease small-cell lung cancer: a phase I study.

BACKGROUND: Irinotecan and cisplatin with concurrent radiotherapy is a powerful treatment combination for patients with limited-disease small-cell lung cancer (LD-SCLC). The objective was to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of irinotecan and cisplatin with concurrent thoracic radiotherapy (TRT) as a once-every-three-weeks schedule. PATIENTS AND METHODS: Patients with LD-SCLC received a fixed-dose of irinotecan (340 mg) and cisplatin (135mg) at day 1 in cycles 1 and 4. During cycles 2 and 3, irinotecan and cisplatin were given in a dose-escalation schedule with concurrent TRT (once daily, total dose 45Gray). RESULTS: No DLT was observed at first two levels (irinotecan 100mg or 120 mg and cisplatin 100mg at day 1 of cycles 2 and 3). In the first five patients, four episodes of grade III diarrhoea/dehydration were observed at cycles 1 and 4. Therefore, from the sixth patient on, fixed-dose irinotecan at cycles 1 and 4 was reduced to 250 mg. At the subsequent level of irinotecan 140 mg and cisplatin 100mg in cycles 2 and 3, two DLTs (severe oesophagitis and late vertebral radiation toxicity) were observed in one patient. CONCLUSION: Irinotecan 140 mg and cisplatin 100mg with concurrent TRT was considered the MTD. Irinotecan and cisplatin in a once-every-three-weeks schedule is not recommended due to severe toxicity. Irinotecan may be more suited for intermittent weekly administration.

A case of localized Castleman's disease with systemic involvement: treatment and pathogenetic aspects.

A patient is presented who had Castleman's disease with constitutional symptoms, a palpable supraclavicular/ axillar mass, and a microcytic anemia, among other laboratory abnormalities, including elevated levels of interleukin-6. Treatment consisted of irradiation of the involved area, with subsequent disappearance of all symptoms and normalization of the laboratory abnormalities. Iron kinetic studies demonstrated a hypoproliferative erythropoiesis, which normalized after radiotherapy. Hypoproliferative erythopoiesis could not be ascribed to serum inhibitors, since normal burst-forming units were observed in the absence or presence of autologous serum. The role of interleukin-6 in relation to Castleman's disease is highlighted.

Pulmonary function changes in lung-cancer patients treated with radiation with or without carboplatin.

In order to examine changes in pulmonary function in patients with locally advanced non-small-cell lung cancer (NSCLC) before, during, and after standard radiotherapy or combined chemoradiotherapy, we conducted a prospective study involving patients with such cancer, who were treated with radiation alone or with concurrent radiation and carboplatin from October 1992 to February 1994 at the University Hospital in Groningen, the Netherlands. Thirty-five patients were treated. Two patients were excluded because of pulmonary emphysema. Pretreatment values of TLC, VC, the gas-transfer coefficient (Kco), the pulmonary diffusing membrane factor (Dm), and pulmonary capillary blood volume (Vcap) were lower than in normal subjects and patients with chemotherapy-naive germ-cell carcinoma who had a similar pulmonary tumor load as the result of hematogenous metastases. The NSCLC patients' reduced Kco was explained by a decrease in Dm, a measure of alveolar-capillary membrane disturbance, and a similar decrease in Vcap. Pretreatment TLC did not correlate with Vcap or Dm, indicating extra- rather than intrapulmonary vascular and lymphatic obstruction as an explanation for the reduced Vcap and Dm. Locally advanced NSCLC was treated with radiation (n = 16) or combined continuous carboplatin infusion and radiation (n = 17). No changes in TLC, VC, Kco, Dm, or Vcap were observed during and 2 wk after the end of either treatment, nor were any differences in pulmonary function observed with the two treatments, indicating an absence of additional acute pulmonary toxicity caused by continuously infused carboplatin in this patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous carboplatin infusion during 6 weeks' radiotherapy in locally inoperable non-small-cell lung cancer: a phase I and pharmacokinetic study.

A phase I study was performed in 21 patients with previously untreated, locally inoperable, non-small-cell lung cancer (NSCLC) with ambulatory continuous carboplatin infusion together with continuous thoracic irradiation over 6 weeks. A dose range for carboplatin of 15 mg m-2 day-1 during the last 21 days (first level), during the last 31 days (second level), or during 6 weeks of the radiation period (third level) and thereafter 20 or 25 mg m-2 day-1 during 6 weeks of radiation (fourth and fifth level) was used. The total radiation dose was 60 Gy given as 2 Gy day-1 for 5 days week-1. The first three patients received radiotherapy without carboplatin. WHO grade III/IV leucopenia and thrombocytopenia occurred in the last two dose levels in two out of six and one out of six patients with 20 mg m-2 day-1 respectively, and in all three patients with 25 mg m-2 day-1 (dose-limiting toxicity). One local infection around the port and a subclavian vein thrombosis occurred. Radiation toxicity of the lung and oesophagus did not seem to be influenced by carboplatin treatment. Out of 21 patients one had a complete response (CR), ten partial response (PR), six stable disease (SD) and four progressive disease (PD). Total (TPt) and ultrafilterable plasma platinum (UPt) were measured in the last three dose levels with atomic absorption spectrophotometry with Zeeman correction. The mean (s.d.) level for TPt for 6 weeks at 15, 20 and 25 mg m-2 day-1 was 0.76 (0.15), 0.78 (0.19) and 0.90 (0.22) mg l-1 for UPt 0.10 (0.03), 0.12 (0.02) and 0.20 (0.03) mg l-1 respectively. TPt concentration levelled off after 3 weeks. The mean (s.d.) CLTB for UPt was 281 +/- 21 ml min-1 and correlated with glomerular filtration rate (r = 0.61, P = 0.03). As estimated with the sigmoid Emax model defined by the Hill equation the percentage reduction in platelets correlated with the area under the curve for UPt (r = 0.77). The maximum tolerable dose of carboplatin with concomitant continuous 60 Gy radiotherapy is 25 mg m-2 day-1; the recommended dose for phase II or III studies is 20 mg m-2 day-1 day for 6 weeks.

Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study.

PURPOSE: To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically proven NSCLC, performance score <2, weight loss <10%, and normal organ functions were randomized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone (both 60 Gy). Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria (NCI CTC) and the Radiation Therapy Oncology Group (RTOG) criteria. Quality of life was measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/LC13 questionnaires. RESULTS: One-hundred and sixty patients were included. Pathologically confirmed persistent tumor was present in 53% of patients in the combination arm versus 58% in the radiotherapy alone arm (P=0.5). Median survival in the combination arm was 11.8 [95% confidence interval (CI) 9.3-14.2] months and in the radiotherapy alone arm 11.7 (95% CI 8.1-15.5) months; progression-free survival was not different between arms [6.8 and 7.5 months, respectively (P=0.28)]. Acute toxicity was mild, late toxicity was radiation-induced cardiomyopathy (three patients) and pulmonary fibrosis (five patients). Quality of life was not different between arms, but in all measured patients cough and dyspnea improved, pain became less, and slight paresthesia developed 3 months after treatment. CONCLUSION: Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival.