Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.

BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.     

Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus

Clinical and Translational Oncology - Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally...     

Blindness in a bladder cancer patient

Abstract Blindness is an unusual symptom in the clinical course of cancer. When it appears it is necessary to differentiate between benign and malign causes. Brain metastases in bladder cancer are extremely rare. MRI is the best diagnostic option. We present a deaf-and-dumb male with subacute blindness, 12 months after the diagnosis of a metastatic bladder cancer. Computerised tomography scan and MRI revealed a mass into the pituitary gland and sella, probably of metastatic origin.     

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-na?ve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.     

Economic evaluation of three two-drug chemotherapy regimens in advanced non-small-cell lung cancer

BACKGROUND: During the 1990s, a number of new cytotoxic agents with clinically relevant activity in non-small-cell lung cancer (NSCLC), and with a more favourable therapeutic index than drugs already in use, became available. Given the high prices of these new drugs and the large number of patients affected, it is important to compare the relative benefits and costs of these treatments with the existing regimens before treatment policy decisions are changed. PURPOSE: An economic evaluation of three different regimens of chemotherapy in patients with advanced NSCLC was performed from the perspective of the Dutch health insurance system using tariffs valid for 2002. The economic evaluation was integrated into a phase III clinical trial in which the reference regimen cisplatin-paclitaxel was compared with two experimental regimens: cisplatin-gemcitabine and gemcitabine-paclitaxel. MATERIALS AND METHODS: Unit costs were applied to resource use data collected prospectively on case report forms during the trial. The average total (uncensored) cost per patient was determined for each of the treatment groups. The principal outcome measure for the economic evaluation was the estimated mean survival time per treatment group. This outcome was then incorporated into incremental cost-effectiveness ratios based on costs corrected for censoring. The impact of uncertainty was assessed by bootstrap techniques, and the analysis and interpretation of the data focused on the bivariate density of differences in outcomes and costs in the incremental cost-effectiveness plane. The final results were summarised by the derivation of cost-effectiveness acceptability curves. RESULTS: The estimated mean survival time was equivalent in the two cisplatin-based regimens with largely overlapping confidence intervals. There was a 99% probability that cisplatin-gemcitabine is the least costly regimen of the two and a 72% probability that this regimen reduces costs while at the same time improving survival. Compared with cisplatin-paclitaxel, the gemcitabine-paclitaxel regimen engendered a borderline significant reduction in mean survival time combined with an almost 90% probability of an increase in costs. CONCLUSION: The two cisplatin-based regimens are equivalent in terms of survival, but cisplatin-gemcitabine may reduce costs by approximately 2000 Euros patient compared with cisplatin-paclitaxel. Gemcitabine-paclitaxel is a dominated option with higher costs and a reduction in mean survival time compared with cisplatin-paclitaxel.     

Incidence of contralateral germ cell testicular tumors in South Europe: report of the experience at 2 Spanish university hospitals and review of the literature

PURPOSE: The crude and cumulative incidence of contralateral germ cell testicular tumors (GCTTs) is between 1% to 5% and 3% to 6% at 10 to 15 years in previously reported studies. To evaluate the real incidence of a second GCTT in a southern European population the medical records of 623 patients with GCTT successfully treated between 1976 and 1993 at 2 university hospitals were reviewed. MATERIALS AND METHODS: All patients had been treated with standard treatment strategies according to disease stage and diagnosis year. Contralateral biopsy at GCTT diagnosis was not performed in any patient. Only those with a survival of 1 year or greater were included. In addition to the imaging and biochemical (tumor markers) procedures used to diagnose disease relapse, physical examination of the contralateral testis and/or testicular ultrasound was done yearly. RESULTS: At a median followup of 8.6 years (range 2 to 19.7) 6 patients (1%) had a contralateral GCTT, which was synchronous in 1 and metachronous in 5. The cumulative risk of a contralateral GCTT was 1.2% (95% CI 0.1% to 2.3%) at 15 years and it did not depend on the treatment for the first GCTT. CONCLUSIONS: The incidence of contralateral GCTT in our series was lower than expected compared with other published series. This finding mirrors the lower incidence of GCTT in the general population in our country than in other areas with a higher incidence of contralateral GCTT. Therefore, contralateral testicular biopsy at initial diagnosis is not mandatory in our experience.     

Brain metastases from renal cell carcinoma. Should we change the current standard?

Renal cell carcinoma (RCC) is one of the most common sources of brain metastases, with an incidence that varies widely from 4% to 48% according to different studies. In addition, asymptomatic metastases occur in up to 33% of patients with metastatic RCC, further complicating the decision-making process in this poor prognosis population. The purpose of this review is to cover in depth the present state of knowledge on the diagnosis and management of patients with brain metastases from RCC, in order to assess whether the current standard should be challenged. The existing systems to predict response and survival will be reviewed, as well as the available therapeutic options regarding local treatment and systemic therapy, all within the context of updated data from clinical trials. In this regard, the role of novel targeted agents for the treatment of brain metastases from RCC, such as the multi-targeted receptor tyrosine kinase inhibitors sunitinib and sorafenib, will be updated and discussed.     

Physical symptoms and psychological distress among patients with HIV infection

There are many questions about the relationship between HIV-related symptoms and psychological distress, and how this relationship affects the immunological and clinical stage of illness. This article reviews the most recent research studies in this field, and encourages new research projects which will help in the management of physical and psychological symptoms associated with HIV infection.     

Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin-based combination chemotherapy

Background: Primary mediastinal non-seminomatous germ cell tumours (MNSGCT)constitute a rare malignancy. This study was performed to review ourexperience with cispatin-based chemotherapy in patients with MNSGCT.Patients and methods: Patients with MNSGCT treated with cisplatin-basedcombination chemotherapy between 1978–1995 in three university hospitalsin Spain were retrospectively studied.Results: There were 25 males and two females with a median age of 26 years(range 4–71). Fifteen patients had disease confined to the mediastinumand 12 had metastatic disease. All patients were treated with cisplatinchemotherapy regimens (PVB: 7, BEP: 6, and other regimens 12) and consideredfor residual mass surgery (RMS) when indicated. Eleven patients (40.7%)were rendered disease-free with initial treatment: four with chemotherapyalone, one with surgery plus adjuvant chemotherapy and six with chemotherapyplus RMS. Three of these patients relapsed at two, six and seven months. Theremaining 16 had unfavourable reponses (five partial response, three nochange, seven progressive disease and one toxic death) . Eleven patientsreceived salvage treatment but none of them achieved a durable response. Aftera median follow-up of 77 months (range 1–168), 10 patients remain alive.Actuarial survival at five years is 31.7%. No patients in this seriesdeveloped a haematological malignancy. Chromosomal analysis showed that 2 outof 10 patients (20%) had a 47XXY karyotype.Conclusions: Only patients who achieved disease-free status are likely tobe cured. Therefore, new up-front strategies are needed for the treatment ofMNSGCT.     

A phase II study of a novel gemcitabine plus cisplatin regimen administered every three weeks for advanced non-small-cell lung cancer

Background: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m² and cisplatin was administered at a dose of 100 mg/m² on day 1, every 21 days.Results: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%–82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3–4 in 54% of the patients, and thrombocytopenia grade 3–4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m²/week, and 31 mg/m²/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7–13), 17 patients are still alive and nine have died. The median overall survival is 12 months.Conclusion: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.