Prognostic evaluation in palliative care: final results from a prospective cohort study.

Prognostic characterization in the initial assessment of patients with advanced cancer disease is an essential step to plan the most appropriate therapeutic program. Since clinical prediction of survival (CPS) may be of limited value, some authors have tried to integrate specific prognostic factors into prognostic multidimensional scores. We carried out a prospective cohort study in two palliative care units to compare the accuracy of the Palliative Prognostic (PaP) Score, the Objective Prognostic Score (OPS), and the Palliative Prognostic Index (PPI). In addition, we compared the accuracy of the CPS independently estimated by different healthcare professionals and we tested the role of laboratory results, together with clinical and social factors in predicting survival. Clinical and laboratory data of 334 advanced cancer patients were prospectively collected from the time of in-hospital admission. PaP Score was the most accurate index of survival prediction, followed by PPI; CPS estimates' accuracy was similar among physicians and nurse. All healthcare professionals tended to underestimate the real survival. Integrating CPS with multidimensional indexes may further improve the patient's management. The degree of autonomy and the number of metastatic sites were independent prognostic factors for 30-days mortality and overall survival in multivariate analysis.

Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer.

AIM: To explore the prognostic value of extended mutational profiling for metastatic colorectal cancer (mCRC). MATERIALS & METHODS: We retrospectively reviewed survival results of 194 mCRC patients that were assigned to four molecular subgroups: BRAF mutated; KRAS mutated codons 12-13 only; any of KRAS codons 61-146, PIK3CA or NRAS mutations and all wild-type. Point mutations were investigated by pyrosequencing. RESULTS: BRAF (5.2%) and KRAS 12-13 (31.9%) mutations were associated with poorer survival (HR 2.8 and 1.76, respectively). Presenting with right-sided colon cancer, not resected primary tumor, WBC >10 × 10(9)/l, receiving less chemotherapy or no bevacizumab were all associated with inferior outcome. The all-wild-type subgroup (39.2%) reported the longest survival. CONCLUSION: Extended mutational profile combined with clinical factors may impact on survival in mCRC.

Risk of unplanned visits for colorectal cancer outpatients receiving chemotherapy: a case-crossover study.

AIM: This study was conducted to evaluate the impact of chemotherapy on the risk of unplanned visit in a cohort of colorectal cancer outpatients. Chief complaints for unplanned visits and risk factors for hospital admission were also analyzed. PATIENTS AND METHODS: Clinical data of 229 consecutive colorectal cancer patients who were unexpectedly presented to our acute oncology clinic between 2006 and 2009 were reviewed. A case-crossover statistical analysis was applied to study the association between exposure to chemotherapy (trigger event) and the occurrence of unplanned visit (acute outcome) in three time windows (7, 15, and 21 days from the closest previous chemotherapy treatment). Cox model was used to assess the risk factors for hospitalization. RESULTS: There were 469 unplanned visits registered. Most of the patients had Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (80 %) and advanced cancer stage (78 %). The majority of unplanned visits (72 %) occurred within 30 days since last chemotherapy. The most frequent presenting complaints were pain, fatigue, and anorexia. The two time windows associated with higher risk of visit were 15 and 21 days from last treatment, both for early (odds ratio [OR] 3.8, CI 1.4-10.2 and OR 3.8, CI 1.4-10.2) and advanced disease stage (OR 1.71, CI 1-2.9 and OR 3, CI 1.5-5.9). Of the unplanned visits, 10 % resulted in hospital admission. Presenting with multiple symptoms and with deteriorated PS were both predictors for hospitalization. CONCLUSION: Chemotherapy exposition triggers the need for unplanned visits over the second and third week after treatment. The prompt and effective management of unexpected events may be cost- and time-saving and reduce pressure on oncology services.

Biglycan expression and clinical outcome in patients with pancreatic adenocarcinoma.

Conflicting results have been reported on the role of extracellular matrix (ECM) proteins in pancreatic cancer. Preclinical studies suggest that the overexpression of biglycan (proteoglycan-I, PG-I), a leucine-rich protein of the ECM, may induce growth arrest of pancreatic cancer cells. The aim of this study was to assess the prognostic role of biglycan expression in pancreatic cancer. We also evaluated MIB-1 and COX-2 expressions (as potential markers of growth and aggressiveness) to better characterize the biology of the tumors. The classical pathological parameters (grading, desmoplasia, perineural, or vascular invasion) as well as molecular determinants of prognosis were examined. MIB-1 (a proliferative index associated with prognosis in most tumors), COX-2, and PG-I expressions were detected by immunohistochemistry and immunofluorescence on tissue samples from 53 patients with pancreatic cancer and reviewed by two independent pathologists. To verify PG-I expression, three rabbit sera (LF104, LF112, and LF121 from NIH, Bethesda, MA, US) were tested. Logrank test and Cox's model were applied for statistical analysis. Out of 53 patients, 40 had stage III and IV pancreatic cancer. Fourteen patients did not express any of the PG-I epitopes. The patients who expressed at least two PG-I epitopes had shorter survival compared to those with single epitope or lacking any expression (28 vs 44 weeks, P = 0.0021). The MIB-1 higher expression predicted shorter survival (25 vs 41 weeks, P = 0.0059). The other parameters were not associated with clinical outcome. Multivariate analyses confirmed PG-I expression and MIB-1 as independent negative prognostic factors. Patients who presented PG-I expression in the ECM had the worse prognosis compared to those who did not. Our results are not in contrast with the hypothesis that ECM proteins are a potential barrier to metastatic spread in localized pancreatic cancer. Rather, we underline the complexity of tumor-stroma interactions in the advanced stage of cancer and the need of further study.

Pharmacology and therapeutic efficacy of capecitabine: focus on breast and colorectal cancer.

Capecitabine (N -pentyloxycarbonyl-5-deoxy-5-fluorocytidine), an oral prodrug of 5-fluorouracil, has provided compelling efficacy data for the treatment of metastatic breast cancer and stage III or IV colorectal cancer, both as monotherapy and in combination regimens. The preferential conversion of capecitabine to 5-fluorouracil in neoplastic tissues renders this fluoropyrimidine particularly appealing for clinical use. The enzyme thymidine phosphorylase, which mediates the final step of the capecitabine activation pathway, is expressed in higher concentration in neoplastic than in healthy tissues. This makes capecitabine more tumor specific than other chemotherapeutic agents. Accordingly, capecitabine is generally well tolerated. In particular, the incidence of myelosuppression and alopecia is low, and the most common side effects, hand-foot syndrome and diarrhea, are usually manageable. Given its good toxicity profile, capecitabine was assessed in combination with several chemotherapeutic or biologic agents. In addition, the observation that thymidine phosphorylase is upregulated after treatment with other anticancer drugs, namely taxanes, provided a rationale for the prominent antitumor activity recently observed for the combination of capecitabine with these agents. This review provides an evidence-based update of clinical trials investigating the role of capecitabine in the treatment of breast and colorectal cancer, with special emphasis on pharmacological and safety issues that form the basis of currently used schedules.

Erlotinib-associated interstitial lung disease in advanced pancreatic carcinoma: a case report and literature review.

The combination of erlotinib and gemcitabine is a recognized option for patients with metastatic pancreatic cancer whose common adverse events such as skin rash, diarrhea, or fatigue are usually easily manageable. Interstitial lung disease (ILD) is a life-threatening toxicity reported in patients with non-small-cell lung cancers treated with epidermal growth factor receptor-tyrosine kinase inhibitors or gemcitabine. This side effect is extremely rare in patients with pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67-year-old patient with metastatic pancreatic cancer. Risk factors and pathophysiology of ILD need further investigation but caution is highly recommended for patients with an underlying pulmonary disease when using erlotinib in monotherapy or combination therapy.