Biomedical subjects

S Cascinu

Publications and source records attributed to S Cascinu.

At least 37 records · Page 2Linked to original sources

PubMed2002

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.

Aged↗

PubMed2002

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.

Adult↗

PubMed2002

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.

Aged↗

PubMed2002

HER-2/neu amplification detected by fluorescence in situ hybridization in fine needle aspirates from primary breast cancer.

BACKGROUND: The HER-2/neu gene is amplified in 20-30% of human breast cancers and has been shown to have prognostic and predictive value for treatment with chemotherapy, hormone therapy and antibodies against the HER-2/neu domain (trastuzumab). The aim of our study was to evaluate the reliability of HER-2/neu determination by fluorescence in situ hybridization (FISH) on fine-needle aspirates (FNAs) from primary breast cancer patients by comparison with the results obtained by FISH and immunohistochemistry (IHC) on the corresponding histological sections. MATERIALS AND METHODS: HER-2/neu amplification was determined by FISH on 66 breast cancer FNAs. Twenty-three and 36 corresponding formalin-fixed, paraffin-embedded sections were assayed by FISH and by IHC, respectively, in order to detect HER-2/neu amplification and HER-2/neu protein expression. RESULTS: Twenty-seven per cent (18/66) of breast cancer FNAs showed amplification of HER-2/neu by FISH. Paired results by FISH cytology and FISH histology were available in 22 cases. Concordance was 91% (20/22). Paired results by FISH cytology and IHC were available in 36 cases. Concordance was 92% (33/36). Eighteen of 66 breast cancer FNAs were also submitted to flow cytometric DNA analysis. None of the diploid cases showed HER-2/neu amplification by FISH. Six out of the eight aneuploid cases were amplified and two were polysomic. CONCLUSIONS: HER-2/neu gene amplification can be reliably estimated by FISH on breast cancer FNAs and a good correlation has been found between FISH and IHC results from the corresponding histological sections.

Biopsy, Needle↗

PubMed2002

Thymidylate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil.

BACKGROUND: Different 5-fluorouracil (5-FU) schedules and/or biochemical modulators may result in different mechanisms of cytotoxicity, potentially affecting the correlation between thymidylate synthase (TS) expression and the clinical response to the fluoropyrimidine. PATIENTS AND METHODS: TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 124 patients homogeneously treated in a series of clinical trials at our institutions with: (A) leucovorin (LV)-modulated infusional 5-FU (n = 48); (B) LV-modulated bolus 5-FU (n = 41); (C) methotrexate (MTX)-modulated bolus 5-FU (n = 35). RESULTS: A statistically significant correlation between TS levels and the clinical response was observed with the regimens involving continuous infusion and/or LV modulation (response rate in patients with low and high TS: 66% versus 24%, P = 0.003, and 50% versus 0%, P = 0.0001, in group A and B, respectively). Conversely, TS levels failed to predict the clinical response within the group of patients treated with MTX-modulated bolus 5-FU (response rate 21% versus 13%, P = 0.50, with low and high TS, respectively). Consistently, the median time to progression/overall survival time in patients with low and high TS were 9 versus 6 months/19 versus 14 months (P = 0.009/0.035, group A), 8 versus 2 months/12 versus 6 months (P = 0.002/0.0006, group B) and 3 versus 2 months/12 versus 13 months (P = 0.14/0.74, group C). CONCLUSIONS: The correlation between intratumoral TS levels and the clinical response to 5-FU depends strongly on the schedule of administration/biochemical modulators that are used in different 5-FU regimens. These data strengthen the notion that different 5-FU schedules have different mechanisms of cytotoxicity.

Adult↗

PubMed2001

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.

Aged↗

PubMed2001

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.

Antineoplastic Agents↗

PubMed2001

Novel therapeutic approaches to cancer patients with bone metastasis.

Bone metastases are a common event in advanced cancer. Breast, lung, prostate and thyroid neoplasms have striking osteotropism. Bone metastatic cancer may be associated with catastrophic consequences for the patients. Therefore, new strategies are warranted in order to reduce the incidence of bone metastases and to palliative established skeletal disease. External beam radiation therapy, endocrine treatments, chemotherapy, bisphosphonates and radioisotopes are all important. Bisphosphonates have become the treatment of choice for tumor-induced hypercalcaemia and more recently they have been used alone or in combination with cytotoxic agents in the palliative treatment of patients with bone metastases. The results are encouraging. Currently, new bisphosphonates that are a hundred times more powerful with respect to clodronate and pamidronate are under investigation. The treatment of metastases to bone and mechanisms of pain relief after radiation therapy are poorly understood. Up to date, there are not standard criteria for the irradiation of bone metastases and bone pain relief may be reached using a variety of fractionation schemes. Radionuclide therapy is the systemic use of radioisotopes for bone pain. It is currently regarded as suitable for comparison with wide-field irradiation, but appears to have major disadvantages in terms of pain relief and toxicity.

Antineoplastic Agents↗

PubMed2001

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.

Adult↗

PubMed2001

Ipsilateral supraclavicular lymph nodes metastases from breast cancer as only site of disseminated disease. Chemotherapy alone vs. induction chemotherapy to radical radiation therapy.

BACKGROUND: To define the role of radiotherapy (RT) in the treatment of ipsilateral supraclavicular lymph-nodes metastases (ISLM) from breast cancer as only site of disseminated disease, we started a prospective non-randomized clinical trial in 1989. Here we report the final results with a median follow-up of 8.75 years. PATIENTS AND METHODS: Thirty-seven patients (pts), with ISLM from breast cancer, were consecutively enrolled into two arms. Arm A (18 pts): chemotherapy (CT) for six courses. Arm B (19 pts): CT for three courses followed by RT to the site of ISLM at 'radical' dose of 50-60 Gy. RESULTS: In arm A, a median Time to Progression (TtP) of 7 months with a median Overall Survival (OS) of 28 months was recorded. In comparison, patients in arm B had a longer median TtP with 20 months as well as a better median OS with 41 months, respectively. An actuarial five-year disease-free survival of 5.5% was obtained in arm A vs. 21% in arm B. A statistically significant difference in TtP was demonstrated between the two groups (P = 0.01). CONCLUSIONS: These data demonstrate that a better event-free survival could be achieved in patients with ISLM submitted to induction CT and radical irradiation. This also translated into a longer survival although this did not achieve statistical significance. We want to stress the importance of local control by RT since it does imply that not all of these patients have micrometastases at the time of relapse in the supraclavicular fossa.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

Inhibition of vascular endothelial growth factor by octreotide in colorectal cancer patients.

Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer; thus its inhibition can arrest tumor growth and decrease metastatic potential. Octreotide has been shown to inhibit growth of colorectal tumors in vitro and in vivo. Part of the antiproliferative activity of octreotide could be related to its antiangiogenic properties. Effects of octreotide on VEGF expression were evaluated in 35 patients with operable colorectal cancer receiving octreotide for 2 weeks before surgery. Tissue VEGF expression and serum VEGF concentrations were determined before and after treatment with octreotide. There was a statistically significant reduction in the tissue VEGF expression both considering the percentage of VEGF positive cells (P = 0.006) and the intensity of VEGF staining (P = 0.003). A similar significant reduction was observed in serum values of VEGF (P = 0.03). The present study indicates that octreotide inhibits expression of VEGF in colorectal cancer patients, and, furthermore, that serum VEGF expression correlates with tissue VEGF, representing a safe method to monitor the activity of antiangiogenic agents.

Aged↗

PubMed2001

Nerve growth factor receptor immunoreactivity in breast cancer patients.

Nerve growth factor receptor (NGF-R) has been shown to have antiproliferative, differentiative, or apoptotic effects on some types of tumor cells, whereas in others it may have mitogenic activity. The immunohistochemical distribution of NGF-R was analyzed in a series of tissue samples from breast cancer patients and its relationship with other clinical and pathological parameters was studied. The distribution of NGF-R was evaluated by immunohistochemistry in frozen tissue samples of 46 breast cancer patients (ME20-4 monoclonal anti-NGF-R). NGF-R immunoreactivity was localized in the plasma membrane of myoepithelial cells, differentiated ducts, neoplastic cells, blood vessels, and nerve fibers in 26 patients (57%). Less differentiated neoplastic tissues were usually NGF-R negative. NGF-R immunoreactivity was associated with estrogen receptor (ER) status (p = 0.02), small tumor dimension (pT) (p = 0.04), low histologic grade (G1-G2) (p < 0.05), old age (p = 0.02), menopause (p = 0.02), and long disease-free survival (DFS) (median follow up 86 months; p = 0.03; independently from ER, pT, age, menopause by multivariate analysis, p = 0.0078). The expression of NGF-R immunoreactivity by breast cancer patients with long DFS may represent a crucial step both in the differentiation status of neoplasia and in the host immune mechanism controlling tumor growth and metastasization.

Age Factors↗

PubMed2001

Survival and quality of life in gastrointestinal tumors: two different end points?

BACKGROUND: In gastrointestinal tumors, the traditional end point of medical treatment was represented mainly by survival. In the last few years, however, there has been an increasing awareness about the role of quality of life. DESIGN: This paper seeks to discuss these two important end points and their relationship in colorectal, gastric, pancreatic and liver cancers. RESULTS: Chemotherapy has doubled survival in comparison with best supportive care in gastrointestinal tumors. A subjective response, represented by a decrease in cancer-related symptoms is expected in about half of the symptomatic patients in colorectal and gastric cancer. In pancreatic cancer, the positive results in terms of clinical benefit helped define the role of chemotherapy. Although clinical benefit does not represent a validated tool to measure quality of life, it can be a first step in the definition of new, simpler tools to assess this end point. The frequent presence of a serious concomitant disease, liver cirrhosis, in patients with hepatocellular carcinoma (HCC) usually prevents the use of chemotherapy in these tumors, which are often treated with locoregional treatments. Unfortunately, their impact on the survival and quality of life of these patients has never been adequately assessed. CONCLUSIONS: In many gastrointestinal cancers, chemotherapy can produce a survival gain and an improvement in the quality of life. Further studies assessing new drugs and/or combinations should focus on these aspects and their relationships. In particular, the impact of treatments of HCC on both survival and quality of life must be investigated by well-designed prospective trials. When assessing the value of a particular anticancer treatment, it is important to consider the impact it may have not only on survival but also on quality of life. This is particularly so for cancer patients, whose life expectancy may be short.

Carcinoma, Hepatocellular↗

PubMed2001

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.

Antineoplastic Agents, Hormonal↗

PubMed2001

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.

Antineoplastic Agents↗

PubMed2000

High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients.

Thirty-seven colorectal cancer patients with grade 1-4 diarrhea (NCICTC) caused by chemotherapy with 5-FU-containing regimens, received oral loperamide at the initial dose of 4 mg followed by 4 mg every 8 h (total dose 16 mg/24 h). Twenty-five patients (69%) were diarrhea-free and were considered to be treatment responders. Eight-four percent of the patients with grade 1 or 2 diarrhea achieved a response, but only 52% of those with grade 3-4 diarrhea. These data seem to suggest that high-dose loperamide is effective in patients with moderate diarrhea and can be regarded as the treatment of choice. The patients with more severe diarrhea did not respond so well, and should, perhaps, be given first-line treatment with more effective drugs, such as somatostatin analogues (e.g., octreotide).

Administration, Oral↗

PubMed2000

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.

Adult↗