Endobronchial metastases from colorectal cancers: natural history and role of interventional bronchoscopy.

BACKGROUND: Endobronchial metastases are rare. The most frequent primary tumors associated with endobronchial involvement are breast, colon and renal cell carcinomas. Metastases from colorectal cancers can be treated either surgically or with chemotherapy in order to improve survival. OBJECTIVES: This paper aims to report the potential role of interventional bronchoscopy in patients with endobronchial metastases from colorectal cancer. METHODS: This retrospective study included 24 patients who underwent an interventional bronchoscopy procedure between 1988 and 2006. All patients had verified tracheobronchial metastases and were treated to relieve their obstruction. Assessment of the natural history of metastatic colorectal carcinoma, therapeutic options and survival associated with endobronchial metastases are reported. RESULTS: Endobronchial metastases occurred at a median of 53 months (range 18-144) following the diagnosis of the primary tumor. Fifty-seven percent of patients had other proven metastases when the endobronchial involvement was diagnosed. All patients had known synchronous pulmonary metastases upon the discovery of tracheobronchial secondary lesions. The most frequently observed symptoms were dyspnea, cough and hemoptysis. Atelectasis was a common radiological finding. In 67% of patients, an interventional bronchoscopy was possible with the primary intent of relieving the obstruction. An endoscopic intervention provided symptomatic relief and an improvement in forced expiratory volume in 1 s. The median overall survival was 70 months (range 23-245) and 14 months once the endobronchial metastase(s) had been diagnosed. CONCLUSION: Endobronchial metastases occur relatively late in patients with a metastatic colorectal neoplasm. Palliative treatment with interventional bronchoscopy to prevent asphyxia is a safe and effective method that may improve the quality of life in these patients.

Use of the monoclonal antibody anti-HER2 trastuzumab in the treatment of metastatic breast cancer: a cost-effectiveness analysis.

BACKGROUND: This open controlled prospective study aimed at evaluating the medical and economical impact of first line chemotherapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Two groups of HER +++ MBC patients were compared: 26 were treated by a combination of trastuzumab and paclitaxel in 4 "prescriber" centers (group A) and 19 patients were treated by any chemotherapy without addition of trastuzumab, in 6 control centers (group B). The cost of chemotherapy and related hospitalizations was taken into account during the first 8 cycles. RESULTS: Forty-five patients, mean age 51 years have been included. The objective response rate was significantly higher in group A (42% vs. 6%, P = 0.036). The median overall survival was 17 months longer in the group A (29 vs. 12 months). The median progression free survival rate was 12.2 months longer in the group A (19 vs. 7 months). The 1-year survival rate was 85% in the group A and 47% in the group B. The mean overall care cost was 33.271 euro per patient in group A versus 11.191 euro per patient in group B. The additional cost per saved year of life expressed as the incremental cost-effectiveness ratio is 15.370 euro 2002. CONCLUSION: The related additional cost seems affordable for an European health care system and justifies the recommendation for its use in the subpopulation overexpressing HER2.

Etoposide pharmacokinetics and survival in patients with small cell lung cancer: a multicentre study.

PURPOSE: To investigate the prognostic value of systemic exposure to etoposide (Area Under the concentration Curve (AUC(VP16))) on overall survival (OS) in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Data from 52 patients with limited stage (n=17) or metastatic (n=35) SCLC were analysed. They received at least two courses of etoposide (120mg/(m(2)day) on 3 days) combined with either doxorubicin-ifosfamide (AVI, n=29) or platinum compounds (carboplatin: n=16; cisplatin: n=7). Population pharmacokinetic-pharmacodynamic (PK-PD) study was performed using NON-linear Mixed Effect Model (NONMEM) and Splus software with univariate and multivariate analyses. RESULTS: Etoposide plasma concentration vs. time was described by a two compartment model. Etoposide clearance (CL) was significantly dependant on serum creatinine (Scr). Ifosfamide (IFO) coadministration increased etoposide clearance by 28% (median CL(VP16): 2.42L/h vs. 1.89L/h, p<0.0005) leading to a reduced systemic exposure (median AUC(VP16): 260mgh/L vs. 339mgh/L). No influence of body surface area (BSA) on CL(VP16) was observed. Median percent decrease of absolute neutrophil count (ANC) after the first chemotherapy course was greater when etoposide 24h concentration was above 0.33mg/L (88% vs. 0%, p=0.028). Median OS was significantly longer in patients treated without ifosfamide (11.0 months vs. 7.0 months, p=0.049) and in patients with CL(VP16)<2.22L/h (14 months vs. 7 months, p=0.013) and AUC(VP16)>254.8mgh/L (11 months vs. 7 months, p=0.048). The independent prognostic factors regarding OS were LDH, CL(VP16) and AUC(VP16). CONCLUSION: In this study it was found that CL(VP16) is reduced in patients with elevated serum creatinine, whilst ifosfamide coadministration increases CL(VP16) and reduces AUC(VP16), demonstrating the interaction between VP16 and ifosfamide. CL(VP16) and AUC(VP16) correlate significantly with overall survival of patients with SCLC patients receiving etoposide regimens.

Advantages of prostate-specific antigen (PSA) clearance model over simple PSA half-life computation to describe PSA decrease after prostate adenomectomy.

OBJECTIVES: A population kinetic approach based on PSA clearance (CL(PSA)) may be a more rational strategy to characterize prostate-specific antigen (PSA) decrease profile after prostate surgery than the commonly used method (half-life from mono/bi-exponential models). METHODS: We used 182 post-adenomectomy PSA concentrations from 56 benign prostatic hyperplasia patients to build, with NONMEM software, a multi-exponential and a CL(PSA) model for comparison. RESULTS: The best multi-exponential model was PSA(t)=4.96e(-)(0.269t)+3.10e(-)(0.16t)+0.746e(+)(0.0002t) with a stable median residual PSA at 0.64 ng/mL. The best model parametrized with clearance was CL(PSA)=0.0229()(AGE/69)(3.78). Akaike information criteria and standard errors favored the CL(PSA) model. Median peripheral zone and transitional zone productions were 0.034 ng/mL/cm(3) and 0.136 ng/mL/g. A threshold at 2 ng/mL on day 90 allowed for a diagnostic of biochemical relapse diagnostic. CONCLUSIONS: The population CL(PSA) model was superior to the multi-exponential approach for investigating individual post-adenomectomy PSA decreases.