Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer.

BACKGROUND: Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. PATIENTS AND METHODS: This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. RESULTS: MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. CONCLUSIONS: For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.

Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy.

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin 50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy

Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial.

BACKGROUND: Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time. METHODS: Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule. RESULTS: A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%-56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 - 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 - 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 - 11.82). CONCLUSION: OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.

Over-DI dissection may question the value of radiotherapy as a part of an adjuvant programme in high-risk radically resected gastric cancer patients.

The aim of our analysis was to assess retrospectively the effect on local relapse, overall survival (OS) and disease-free survival (DFS) of a limited or an extended lymphadenectomy in radically resected gastric cancer patients. This study was performed in order to identify a subgroup of patients possibly not benefiting from a therapeutic approach such as chemoradiation therapy. We divided our patients into two groups according to lymphadenectomy type: group A for limited (<25 resected lymph nodes) and group B for extended (>25 resected lymph nodes) lymph nodes resection. A total of 418 patients were analysed: tumour stage at diagnosis was pT2-3 pN1-3 M0 in 339 patients and pT3 N0 M0 in 79 patients. Median age at diagnosis was 68 years (range 30-92 years). A total of 306 patients (73.2%) were in group A and 112 (26.8%) in group B. The median survival time (OS) for patients in groups A and B was 58.8 and 84.8 months, respectively (P=0.0371); median DFS was 28.8 months in group A and 59.9 months in group B (P=0.0027). At multivariate analysis, extension within the gastric wall, nodal involvement and the number of resected lymph nodes appeared to affect both OS and DFS. An inadequate lymph nodes resection can affect survival and result in a higher incidence of local relapse, making the latter group of patients optimal candidates for adjuvant chemoradiation.

Raltitrexed plus oxaliplatin (TOMOX) as first-line chemotherapy for metastatic colorectal cancer. A phase II study of the Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD).

BACKGROUND: To evaluate the safety and efficacy of the novel raltitrexed/oxaliplatin combination (TOMOX) as first-line chemotherapy for patients with advanced colorectal cancer. MATERIALS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 3 mg/m2 plus oxaliplatin 100 mg/m2, both intravenously, on day 1 every 3 weeks. Patients were re-evaluated after every third cycle and chemotherapy was continued up to tolerance or disease progression. RESULTS: Fifty-eight patients from 13 Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD) centers were accrued from September 1999 to November 2000. According to the intention-to-treat analysis from 58 patients, the overall response rate was 50% [95% confidence interval (CI) 38% to 62%], with three complete responses and 26 partial responses. The median overall survival (44 patients currently alive) was >9 months and the median time to disease progression was 6.5 months (range 1-15 months). The main hematological toxicity was grade III/IV neutropenia, which occurred in 17% of patients, while anemia and thrombocytopenia were uncommon. Grade III/IV non-hematological toxicities were transient transaminitis (17% of patients); asthenia (16% of patients); neurotoxicity (10% of patients) and diarrhea (7% of patients). No toxic death was observed, one patient with grade IV asthenia after the first cycle refused chemotherapy. CONCLUSIONS: The results of this study suggest that the TOMOX combination is an effective and well tolerated regimen for the treatment of advanced colorectal cancer. Its ease of administration and patient tolerance warrant further investigation as an alternative to fluoropyrimidine-based regimens with repeated and prolonged fluorouracil infusions.

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients.

Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (+/-6.4; standard deviation) and the mean plasma carnitine value was 20.9 microM (+/-6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (+/-5.4; standard deviation) (P<.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study.

An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation.

Tumours of patients with node-positive rectal cancer were studied by immunohistochemistry for p53, BAX and vascular endothelial growth factor expressions. Results were correlated to the relapse rate, the pattern of relapse and the event-free survival after radical surgery and adjuvant chemoradiation. After a median follow-up of 60 months, 39 patients remained disease-free and 40 patients relapsed (18 local relapses and 22 distant metastases). The majority of disease-free patients showed p53 negative and vascular endothelial growth factor negative tumours. Local relapses occurred more frequently in patients with p53 overexpressing tumours (P<0.01), while distant metastases were in patients with vascular endothelial growth factor positive tumours (P<0.003). Patients with p53 negative or vascular endothelial growth factor negative tumours showed better event-free survival than patients with p53 positive or vascular endothelial growth factor positive tumours. BAX analysis did not show any association with patients' outcome and it was unrelated to the p53 status. Adjuvant treatment strategies for node-positive rectal cancer may be improved by identifying categories of high-risk patients. In this study, vascular endothelial growth factor and p53 expressions correlated with recurrent disease, pattern of relapse and poor event-free survival.

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: a low cost effective regimen.

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m(-2) i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m(-2) i.v. followed by 5-fluorouracil 400 mg m(-2) i.v. bolus and 600 mg m(-2) i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m(-2) i.v. bolus on day 2, every 6 weeks. Grades 3-4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1-61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.

A systematic review of the role of pulmonary irradiation in the management of primary bone tumours.

INTRODUCTION: Adjuvant therapy in osteosarcoma (OS) and Ewing's sarcoma (ES) is primarily directed towards treatment of subclinical lung disease. Before the advent of modern intensive chemotherapy, lung irradiation was the only available adjuvant treatment. It has proven biological activity and low morbidity. There is, however, a wide variation in its application between centres. This systematic review aims to define the evidence to support the use of lung irradiation in these diseases. DESIGN: A review of trials published between 1966 and 2000 was undertaken to determine the evidence for the use of pulmonary irradiation in OS and ES. RESULTS: Several small series of prophylactic lung irradiation (PLI) have been reported, most from over 20 years ago. These studies support the theoretical basis for the use of PLI in both OS and ES. Few randomised studies have been performed which include PLI. In OS, studies demonstrated a trend in favour of PLI compared with no adjuvant treatment and, subsequently, a level of benefit similar to that achieved with chemotherapy, but no additive effect. No studies have used PLI in addition to current standard chemotherapy regimens, or evaluated its use after successful metastatectomy. In ES, only one randomised study has addressed the role of PLI, in a comparison with vincristine, actinomycin D and cyclophosphamide combination chemotherapy with or without doxorubicin. Prolonged follow-up favoured four-drug chemotherapy. Retrospective reports from large cooperative groups suggest that the addition of whole-lung radiotherapy (WLRT) improves outcome in ES patients presenting with pulmonary metastases. However, there are no randomised study data to support this. CONCLUSIONS: Further randomised studies are necessary to clarify the role of PLI in addition to current standard chemotherapy regimens, or its use after successful metastasectomy in patients with OS. In patients with localised ES adjuvant chemotherapy appears to be superior to PLI alone, while there is little evidence to support treatment with WLRT in patients who present with pulmonary metastases.

Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer.

BACKGROUND: Loss of activity of tumor suppressor genes is considered a fundamental step in a genetic model of carcinogenesis. Altered expression of the p53 and the Deleted in Colon Cancer (DCC) proteins has been described in gastric cancer and this event may have a role in the development of the disease. According to this hypothesis, we investigated the p53 and the DCC proteins expression in different stages of gastric carcinomas. METHODS: An immunohistochemical analysis for detection of p53 and DCC proteins expression was performed in tumor tissue samples of patients with UICC stage I and II gastric cancer. For the purpose of the analysis, the staining results were related to the pathologic data and compared between stage categories. RESULTS: Ninety-four cases of gastric cancer were analyzed. Disease stage categories were pT1N0 in 23 cases, pT2N0 in 20 cases, pT3N0 in 20 cases and pT1-3 with nodal involvement in 31 cases. Stage pT1-2N0 tumors maintained a positive DCC expression while it was abolished in pT3N0 tumors (p <.001). A significant higher proportion of patients with N2 nodal involvement showed DCC negative tumors. In muscular-invading tumors (pT2-3N0) the majority of cases showed p53 overexpression, whereas a significantly higher proportion of cases confined into the mucosa (pT1N0) showed p53 negative tumors. Also, a higher frequency of p53 overexpression was detected in cases with N1 and N2 metastatic lymph nodal involvement. CONCLUSIONS: Altered expression of both DCC and p53 proteins is detectable in gastric carcinomas. It seems that loss of wild-type p53 gene function and consequent p53 overexpression may be involved in early stages of tumor progression while DCC abnormalities are a late event.

Molecular markers predictive of response to chemotherapy in gastrointestinal tumors.

Gastrointestinal cancers account for a large amount of human tumors. Surgery is the standard treatment for localized gastrointestinal cancer, but in a large number of patients, tumors are unresectable at time of diagnosis and even when resectable, survival is often poor. Current attempts to improve these results include the use of chemotherapy in the adjuvant setting, in the advanced disease, or as neoadjuvant treatment. However, less than half the patients respond to chemotherapeutic treatments, mostly reporting important side-effects. The identification of molecular markers, such as p53, thymidylate synthase, K-ras, and others, may provide an important tool for medical oncologists in defining subsets of patients with gastrointestinal cancers more suitable to benefit from chemotherapy or from experimental therapies. The relationship between the clinical outcome to anticancer drugs and molecular markers in gastrointestinal tumors has been reviewed. Available data are promising, but most of them arise from retrospective and small studies. Well designed, prospective trials are warranted to change the target approach from a general to an individual treatment strategy.

Vascular endothelial growth factor expression, S-phase fraction and thymidylate synthase quantitation in node-positive colon cancer: relationships with tumor recurrence and resistance to adjuvant chemotherapy.

BACKGROUND: The behaviour of colorectal carcinomas may depend on molecular properties of tumors. In node-positive colon cancer, we assessed the S-phase fraction (SPF) index, the vascular endothelial growth factor (VEGF) expression and the TS levels. The combined analysis of SPF/VEGF was studied for predictivity of recurrent disease, the TS quantitation was related to the efficacy of fluorouracil-based adjuvant chemotherapy. PATIENTS AND METHODS: Consecutive patients with surgically-resected, node-positive colon cancer were studied. Flow cytometry for the SPF and immunohistochemistries for the TS and the VEGF expression were carried out on the primary tumor. Recurrences had to be proven by biopsy or surgery, and they were categorized as early, if occurred within 12 months after surgery, or late if occured 13 months or more. RESULTS: Of 150 evaluable patients, 100 had received fluorouracil-based adjuvant chemotherapy and 50 control patients were untreated. The combined analysis of the VEGF and the SPF showed a strong association between the two markers; 48 patients (32%) had high SPF/VEGF positive tumors and 69 patients (46%) had low SPF/VEGF negative tumors (P < 0.0001). The majority of disease-free patients (73.4%) showed VEGF negative/low SPF tumors (P < 0.0001). Early recurrences occurred more frequently in patients with VEGF positive/high SPF tumors (P < 0.001). In the 100 patients treated with adjuvant chemotherapy, 86% of relapsed patients had TS overexpressing tumors and 69% of disease-free patients had TS negative tumors (P < 0.001). Also, early recurrences occurred more frequently in TS overexpressing tumors (P < 0.0001). CONCLUSIONS: Evidence is supported that node-positive colon cancer constitutes a heterogenous disease. Patients with VEGF positive/high SPF tumors showed an unfavourable outcome compared to patients with VEGF negative/low SPF tumors. The efficacy of fluorouracil-based adjuvant chemotherapy may depend on the TS status.

Gastrointestinal cancer refractory to chemotherapy: a role for octreotide?

Although octreotide has been shown to inhibit the growth of gastrointestinal (GI) tumors in vitro and in vivo, preliminary clinical trials have reported disappointing results for this somatostatin analog in patients with GI cancers. The results of these trials probably reflect the difficulty in assessing the therapeutic potential of an agent such as octreotide in GI cancers. Thus, it is possible that treatment with octreotide could be useful in the stabilization of disease if it is associated with an improvement in survival. On the basis of these considerations five randomized trials were carried out to evaluate the therapeutic potential in patients with GI cancers. Four trials (one in patients with colorectal carcinoma and three in patients with carcinoma of the pancreas) did not show any advantage of octreotide in untreated patients; in contrast, one trial reported that octreotide prolonged survival in patients with GI cancers refractory to chemotherapy. Some clinical features of the latter study (treatment with chemotherapy, different schedules) may explain these conflicting results. Although data from randomized trials suggest that octreotide is not effective in untreated asymptomatic advanced GI cancer patients, further studies are warranted to assess the efficacy of octreotide in chemotherapy refractory patients in order to clarify the impact of octreotide in terms of not only survival but also on the patients' quality of life.

A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer.

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy.

Prognostic biomarkers in resected colorectal cancer: implications for adjuvant chemotherapy.

Knowledge of the prognostic role of biomarkers in colorectal cancer is limited and the routine determination for clinical practice is not warranted. However, for some of these markers, data are promising enough for further evaluation. This review addresses a comprehensive analysis of prognostic biomarkers in colorectal cancer. Data from published studies were collected and analyzed. A sufficient level of evidence suggests that DNA indexes, angiogenesis indicators and some genetic/biochemical markers identity prognostic differences in patients with early-stage colorectal cancer. High-risk patients could be the target for future adjuvant chemotherapy trials and one or more of these markers may identify prognostic subgroups with the same TNM stage category.

A phase II study of weekly docetaxel as salvage chemotherapy for advanced gastric cancer.

BACKGROUND: Docetaxel has shown some activity in advanced gastric cancer. Recent phase I studies found low hematologic toxicity and a favourable toxicity profile when docetaxel was administered on a weekly schedule. In this study, we explored the activity of weekly docetaxel in patients with advanced gastric cancer who failed first-line chemotherapy. MATERIALS AND METHODS: Patients with stable or progressing disease after first-line chemotherapy received 36 mg/m2 weekly docetaxel. One cycle consisted of six administrations followed by a two-weeks rest, patients were re-evaluated at week eight. The optimal two-stage design was adopted for early stopping of the trial if responses were one or less in 21 patients (< 20% response rate with alpha and beta error probabilities 0.05 and 0.010 respectively). RESULTS: Twenty-one patients have been enrolled and they are fully evaluable for response and toxicity. One patient achieved partial response, 8 patients had stable disease and 12 patients progressed. Median overall survival from the onset of salvage chemotherapy was 3.5 months. Hematologic toxicity was observed in two patients who experienced grade III leukopenia. Beginning from the third week of treatment, most of the patients (90%) showed grade II asthenia which resulted the commonest side-effect. CONCLUSIONS: This schedule of weekly docetaxel did not show significant activity in pretreated patients with advanced gastric cancer.

Immunohistochemical determination of p53 protein does not predict clinical response in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil-leucovorin combination.

BACKGROUND: We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination. PATIENTS AND METHODS: The study population consisted of 41 patients with unresectable metastatic colon cancer, homogeneously, treated with bolus 5-FU and LV. RESULTS: Twenty-seven patients (66%) showed high levels of TS expression. The difference in the proportion of objective responses between patients with low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27) TS levels was statistically significant (P = 0.0001, chi-square test). p53 nuclear over-expression was found in 27 of 41 patients (66%). No differences were observed in p53 overexpression in patients with high (66%) or low (66%) TS expression. p53 status was not found to be associated with response even in patients with low TS expression. CONCLUSIONS: p53 status measured by immunohistochemistry does not seem to be useful to identify unresponsive patients with low TS expression.

Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer.

The usefulness of chemotherapy in patients with stage II disease continues to be debated. Biological prognostic factors may allow further insight into the optimal treatment strategy for patients with node-negative disease. Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer. Recently, it was shown able to predict disease recurrence in patients with stage II colon cancer. Specimens of surgically resected colon cancer were immunostained for VEGF. Consecutive patients referred to the study institutions were considered eligible for this study. The main inclusion criteria were stage II tumor, sufficient tumor material, and adequate follow-up information. Analysis was performed on 121 patients. The recurrence rate in the patients with VEGF-positive tumors was 50% (18 of 36 patients), which was significantly higher than that observed in patients with VEGF-negative tumors [11.7% (10 of 85 patients); P = 0.001]. Also the degree of VEGF immunoreactivity was significantly higher in 28 relapsing patients compared with 93 disease-free patients (mean VEGF score, 2.84 0.38 versus 0.66 +/- 0.17; P = 0.0001). VEGF may be used in a clinical setting to identify patients at high risk for relapse who may benefit from adjuvant treatment including new therapeutic strategies such as monoclonal antibody neutralizing VEGF.

Prognostic value of S-phase fraction in T3N0M0 gastric cancer. Implications for adjuvant chemotherapy.

INTRODUCTION: The prognosis of patients with T3N0M0 gastric cancer is still unfavourable and the role of adjuvant chemotherapy is unclear. We addressed this study to evaluate whether the analysis of the S-Phase Fraction (SPF) might have prognostic implications in serosa-positive, node-negative gastric cancer. MATERIALS AND METHODS: Specimens of resected gastric cancer were studied by flow cytometry for SPF analysis. Consecutive patients with stage pT3N0M0, adequate follow-up information and sufficient archival tumor tissue were considered eligible for the study. The tumor SPF indices were related to the timing of recurrences, the relapse rate and the disease-free survival of patients. RESULTS: The analysis was carried out on samples of 137 patients with surgically-resected, stage pT3N0M0 gastric cancer. SPF resulted high and low in 39% and 61% of cases, respectively. Fifty-seven patients relapsed (42%) and early recurrences (within 18 months after surgery) occurred more frequently among cases with high SPF (p < .03). Patients with high SPF tumors showed a worse relapse rate and disease-free survival than patients with low SPF tumors. (p < .005). CONCLUSION: The SPF analysis showed prognostic differences among patients with stage pT3N0M0 gastric cancer. These data may be of value in the planning of future adjuvant chemotherapy trials in gastric cancer.