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2.
Tech Coloproctol ; 21(8): 633-640, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28755256

ABSTRACT

BACKGROUND: Rectum-sparing approaches appear to be appropriate in rectal cancer patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The aim of the present study is to evaluate the effectiveness of rectum-sparing approaches at 2 years after the completion of neoadjuvant treatment. STUDY DESIGN: Patients with rectal adenocarcinoma eligible to receive neoadjuvant therapy will be prospectively enrolled. Patients will be restaged 7-8 weeks after the completion of neoadjuvant therapy and those with mCR (defined as absence of mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with mCR will undergo local excision, while patients with cCR will either undergo local excision or watch and wait policy. The main end point of the study is to determine the percentage of rectum preservation at 2 years in the enrolled patients. CONCLUSION: This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).


Subject(s)
Adenocarcinoma/therapy , Rectal Neoplasms/therapy , Watchful Waiting , Adenocarcinoma/surgery , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Humans , Neoadjuvant Therapy , Organ Sparing Treatments , Preoperative Period , Radiotherapy, Adjuvant , Rectal Neoplasms/surgery , Rectum , Research Design
3.
Eur J Surg Oncol ; 40(10): 1165-76, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25239441

ABSTRACT

Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is increasing throughout the world, and is particularly high in the human immunodeficiency virus positive (HIV+) population. A multidisciplinary approach is mandatory (involving radiation therapists, medical oncologists, surgeons, radiologists and pathologists). SCCA usually spreads in a loco-regional manner within and outside the anal canal. Lymph node involvement at diagnosis is observed in 30%-40% of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5%-8% at onset, and rates of metastatic progression after primary treatment between 10 and 20%. SCCA is strongly associated with human papilloma virus (HPV, types 16-18) infection. The primary aim of treatment is to achieve cure with loco-regional control and preservation of anal function, with the best possible quality of life. Treatment dramatically differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based chemoradiation and other cytotoxic agents (mitomycin C) have been established as the standard of care, leading to complete tumour regression in 80%-90% of patients with locoregional failures in the region of 15%. There is an accepted role for surgical salvage. Assessment and treatment should be carried out in specialised centres treating a high number of patients as early as possible in the clinical diagnosis. To date, the limited evidence from only 6 randomised trials [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural history depending on the predominant site of origin, (the anal margin, anal canal or above the dentate line) provide scanty direction for any individual oncologist. Here we aim to provide guidelines which can assist medical, radiation and surgical oncologists in the practical management of this unusual cancer.


Subject(s)
Anus Neoplasms/diagnosis , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Medical Oncology/standards , Anus Neoplasms/virology , Carcinoma, Squamous Cell/virology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Prognosis , Societies, Medical
5.
Ann Oncol ; 22(11): 2424-2430, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21385884

ABSTRACT

BACKGROUND: The aim of this phase II study was to assess the activity of panitumumab in combination with oxaliplatin, 5-fluorouracil, and external radiotherapy (RT) as preoperative treatment in locally advanced rectal cancer patients. PATIENTS AND METHODS: Patients had rectal adenocarcinoma, cT3N+ or cT4N-/+ stage, located <12 cm from the anal margin. Panitumumab was administered before the start of chemo-RT, and every 2 weeks in combination with 5-fluorouracil-oxaliplatin with concurrent RT. Rectal surgery was carried out 7-8 weeks after the end of neoadjuvant treatment. The primary end point was a pathological complete response rate of 25%. RESULTS: Sixty patients were enrolled from February 2007 to October 2009. Fifty-five (91.7%) patients underwent surgery. Rate of pathological complete response was 21.1% (95% confidence interval 10.4% to 31.6%). Pathological downstaging occurred in 33 of 57 (57.9%) patients. Grade 3-4 toxicity during neoadjuvant treatment was diarrhea (38.9%), cutaneous reactions (18.6%), nausea (5.1%), asthenia (3.4%), anorexia (3.4%), and neutropenia (1.7%). One toxic death was observed for diarrhea. CONCLUSIONS: In our study, the primary end point is not reached and panitumumab combination treatment was associated with high incidence of grade 3-4 diarrhea. The higher pathological complete response rate in comparison with the results of previous neoadjuvant rectal cancer trials with anti-epidermal growth factor receptor monoclonal antibodies supports further studies necessary to understand the possibility of optimal regimens and sequences with chemo-RT.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/genetics , Diarrhea/chemically induced , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Mutation , Neoadjuvant Therapy , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Panitumumab , Positron-Emission Tomography , Preoperative Care , Rectal Neoplasms/genetics , Rectal Neoplasms/surgery
8.
Eur J Surg Oncol ; 32(10): 1201-8, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16872799

ABSTRACT

AIMS: To investigate early and late complications in 44 patients with locally advanced mid-low rectal cancer enrolled in a phase I-II study, who had received an aggressive chemoradiation treatment (50.4Gy/28F; 5-FU continuous infusion and weekly Oxaliplatin) followed by total mesorectal excision and 5-FU based postoperative chemotherapy. The aim of the present study is also to evaluate functional outcome and quality of life (QoL) in a sub-group of 22 patients. METHODS: Standardized forms for early and late surgical complications were completed for all patients. Anorectal function and QoL were also investigated in 22 patients who underwent surgery in the same surgical unit, using the fecal incontinence scoring system (FIS) and EORTC-QLQ-CR38 questionnaires, compiled before and after radiotherapy and at least 8 months after surgery. The differences over time in scores were analyzed using repeated measure ANOVA. RESULTS: The median age of patients (25 males and 19 females) was 58 (range: 34-73) years. A low anterior resection was performed in 39 cases, radical resection in 41, and 12 patients had a pathological complete response. There were no operative deaths; 4 and 9 patients required re-operation for early and late complications, respectively. FIS score did not present a significant worsening over time. According to data in the EORTC-QLQ-CR38 questionnaire, a significant improvement over time was found only for "future perspective". CONCLUSION: Our findings seem to indicate that this aggressive 5-FU-Oxalipaltin-based treatment implies no impairment of QoL and anorectal function, even if a high rate of late major complications was observed. Studies on larger series are required to confirm these results.


Subject(s)
Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy , Postoperative Complications , Quality of Life , Rectal Neoplasms/surgery , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Fecal Incontinence/etiology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Rectum/surgery , Surveys and Questionnaires
10.
Ann Oncol ; 16(7): 1140-6, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15894548

ABSTRACT

BACKGROUND: Oxaliplatin (OXA) significantly enhanced the antitumour activity of 5-fluorouracil (FUra) in patients with advanced colorectal cancer and displayed radiosensitising properties in preclinical studies. This study was thus performed to test the feasibility, identify the recommended doses (RDs) and explore preliminarily the clinical activity of weekly OXA and infused FUra combined with preoperative pelvic radiotherapy. PATIENTS AND METHODS: Forty-six patients with recurrent or locally advanced (cT3-4 and/or N+) adenocarcinomas of the mid-low rectum were treated with escalating doses of OXA (25, 35, 45, 60 mg/m2, weekly for 6 weeks) and FUra (200-225 mg/m2/day, 6-week infusion) concurrent to preoperative pelvic radiotherapy (50.4 Gy/28 fractions). The RDs for the phase II part of the study were immediately below the level resulting in dose-limiting toxicities in more than one third of the patients, or corresponded to the last planned dose level. RESULTS: In the escalation phase, dose-limiting toxicities only occurred in one patient at the fourth level and one of six patients treated at the last planned dose level (grade III diarrhoea). OXA 60 mg/m2 and FUra 225 mg/m2/day are therefore the RDs for the regimen. Among 25 patients globally treated at these doses (phase II part), the incidence of grade III diarrhoea was 16% with no grade IV toxicity. Neurotoxicity did not exceed grade II (12%). All patients completed radiotherapy and were operated on as scheduled. Twenty-one of 25 patients had the tumour down-staged after chemoradiation with seven (28%) pathological complete responses and 12 (48%) residual tumours limited to ypT1-2N0. CONCLUSIONS: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cohort Studies , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Preoperative Care
11.
Eur J Cancer ; 40(12): 1872-7, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15288289

ABSTRACT

BBR3464, a novel tri-nuclear platinum complex, forms long-range DNA adducts and is highly potent when compared with cisplatin in vitro. Preclinical studies demonstrated activity in cisplatin-resistant tumours and tumours with mutated p53 status. Phase I & II clinical studies gave preliminary indications of activity in melanoma, pancreatic, lung and ovarian cancers. The aim of this study was to determine the efficacy and confirm the toxicity of BBR3464 when given either as first- or second-line treatment for advanced disease in patients with gastric and gastro-oesphageal adenocarcinoma. Two multicentre, open label, Gehan design studies were conducted; one study used BBR3464 as first-line and the other as second-line treatment for metastatic or locally advanced disease. Nineteen first-line and 26 second-line patients were enrolled receiving a total of 74 and 53 infusions, respectively. Initially, seven patients in the second-line study received BBR3464 using the planned schedule of 1.1 mg/m2 every 4 weeks; however, 5 of these patients experienced dose-limiting grade 3 or 4 febrile neutropenia; subsequent patients in both studies were treated using the modified schedule of 0.9 mg/m2, every 21 days. In 1 of 17 evaluable, previously untreated patients, regression of multiple skin lesions was noted with stabilisation of lung metastases and maxillary sinus mass, lasting 155 days. In the first-line study, the median time to progression was 85 days [95% Confidence Interval (CI): 42, 127] (2.8 months) and in the second-line study, the median time to progression was 71 days [95% CI: 42, 109] and 38 days [95% CI: 32, 73] in the 1.1 and 0.9 mg/m2 dose level groups, respectively. Toxicity data were available for 45 patients. Neutropenia was the main toxicity seen (G3: 40%, G4: 40%). Febrile neutropenia was observed in six patients (15%) treated with 0.9 mg/m2 compared with five patients (71%) treated with 1.1 mg/m2 BBR3464. Other drug-related toxicities (G3/4) included: anaemia, thrombocytopenia, nausea, vomiting, diarrhoea, mucositis and fatigue. Diarrhoea and nausea/ vomiting were adequately controlled by the use of loperamide and antiemetics, respectively. Recruitment to the second-line study was closed early due to the poor response rate (1/17 evaluable, 6%; 95% CI: 1%, 27%) and short time to progression noted in the first-line study. Further studies with BBR3464 in this tumour type are not recommended.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Esophageal Neoplasms/drug therapy , Organoplatinum Compounds/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged
12.
Ann Oncol ; 15(1): 55-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14679120

ABSTRACT

BACKGROUND: The level of the enzyme thymidylate synthase (TS) is known to inversely correlate with the clinical activity of 5-fluorouracil (FU) in advanced colorectal cancer patients. Since the correlation is not very strong, we have retrospectively analyzed the expression of E2F-1 in tumor samples or metastases from 25 patients with advanced colorectal cancer, homogeneously treated with an FU-based regimen. E2F-1 is a transcription factor regulating the expression of TS along with other crucial DNA synthesis related enzymes. MATERIALS AND METHODS: E2F-1 expression was analyzed by immunohistochemistry using the anti-E2F-1 monoclonal antibody KH95, scoring 2000 cells/case. Expression of TS was evaluated by immunohistochemistry using a rabbit anti-human polyclonal antibody. RESULTS: The level of E2F-1 expression did not correlate with TS expression, although a trend for correlation between E2F-1 level and maximal tumor shrinkage was observed (r = 0.42; P = 0.054). CONCLUSIONS: In spite of previous reports demonstrating that E2F-1 quantified by rt-PCR and western blot correlates with TS and could be used as a predictor to select colorectal cancer patients more likely to respond to FU treatment, our data suggest that, under these experimental conditions, immunohistochemistry cannot be used for such selection.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Cell Cycle Proteins , Colorectal Neoplasms/drug therapy , DNA-Binding Proteins , Fluorouracil/pharmacology , Thymidylate Synthase/metabolism , Transcription Factors/metabolism , Animals , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , E2F Transcription Factors , E2F1 Transcription Factor , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Immunohistochemistry , Rabbits , Sensitivity and Specificity , Statistics as Topic , Thymidylate Synthase/immunology , Transcription Factors/immunology , Transcription, Genetic , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/enzymology
13.
Colorectal Dis ; 5 Suppl 3: 29-35, 2003 Nov.
Article in English | MEDLINE | ID: mdl-23573558

ABSTRACT

Radiation therapy is well established in the treatment of early and locally advanced rectal cancer, where it has been used in both the pre-operative and postoperative settings. Pre-operatively, radiation therapy has been shown in a series of studies culminating in the Dutch total mesorectal excision (TME) study to significantly reduce the rate of local recurrence at 2 years. However, the overall rate of survival was not improved in this study because radiotherapy failed to reduce the incidence of distant metastases. Chemotherapy, however, may reduce distant metastatic spread, as well as increasing the rate of R0 resectability and sphincter-saving surgery when used in combination with radiotherapy in the neoadjuvant setting. Oxaliplatin is a prime candidate for radiochemotherapy in rectal cancer because it frequently has large and rapid cytoreductive effects in colorectal malignancies and has been shown in vitro and preclinical models to be radiosensitizing. In an Italian phase I/II study, weekly oxaliplatin combined with standard infusional 5-FU and pre-operative radiotherapy has shown low toxicity and promising antitumour activity. These encouraging results are now being followed up in a more extensive trials programme. A randomized trial comparing this regimen with standard infusional FUra and radiotherapy (STAR, Studio nazonaleTerapia neoAdiuvante Retto [National Study on Neoadjuvant Treatment of Rectal cancer]) is being launched in Italy. A new phase II study, CORE (Capecitabine, Oxaliplatin, Radiotherapy and Excision), is now in development in Europe and will use a similar weekly treatment regimen with an oral fluropyrimidine in place of infusional FUra, and a number of further oxaliplatin-based radiochemotherapy studies in rectal cancer are planned or in progress. In summary, radiochemotherapy appears to have the potential to significantly improve clinical outcomes in rectal cancer, and oxaliplatin-based treatment is proving central to its ongoing development.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/methods , Organoplatinum Compounds/administration & dosage , Rectal Neoplasms/therapy , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Digestive System Surgical Procedures , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Neoplasm Staging , Oxaliplatin , Radiotherapy Dosage , Rectal Neoplasms/pathology , Survival Rate
14.
Ann Oncol ; 13(12): 1882-92, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12453856

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/analysis , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/enzymology , Thymidylate Synthase/metabolism , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Chi-Square Distribution , Cohort Studies , Colorectal Neoplasms/pathology , Evaluation Studies as Topic , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , Leucovorin/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Predictive Value of Tests , Probability , Prognosis , Sensitivity and Specificity , Survival Rate , Thymidylate Synthase/analysis , Treatment Outcome
15.
Cancer Treat Rev ; 28(1): 27-47, 2002 Feb.
Article in English | MEDLINE | ID: mdl-12027413

ABSTRACT

Thymidylate Synthase (TS) is a rate-limiting enzyme in the DNA synthetic pathway and represents the cellular target of the antimetabolite drug 5-fluorouracil (FUra). Both preclinical and clinical studies have shown that the level of expression of this enzyme and the ability to achieve its inhibition are the major determinants of sensitivity and resistance to fluoropyrimidines (FP). In particular, five recent studies have consistently demonstrated an inverse correlation between the level of TS gene or protein expression measured in colorectal cancer metastases and the clinical response to either FUra or 5-fluorodeoxyuridine (FUdR). Patients with low levels of TS expression in their metastases have indeed shown response rates that are three to ten times higher compared to those obtained in patients with high TS levels. The independent predictive value demonstrated in a logistic regression model, the longer survival shown by patients with low TS levels in three of five studies and the consistency of the results obtained by independent groups using different techniques to quantitate TS expression, strengthen the predictive role of TS. Targeted treatment of colorectal cancer based on TS quantitation has thus been hypothesized similar to the use of hormone receptor in breast cancer. In this review preclinical and clinical data supporting the use of TS quantitation to predict for the clinical response to FUra will be described and unresolved problems including assays standardization, response prediction based on TS levels measured in primary tumors, intrapatient variations in TS levels and biological/biochemical limitations of this strategy will be discussed.


Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm , Floxuridine/pharmacology , Fluorouracil/pharmacology , Thymidylate Synthase/metabolism , Cytological Techniques , Humans , In Vitro Techniques , Predictive Value of Tests , Reference Standards
17.
Br J Cancer ; 84(8): 1023-8, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11308248

ABSTRACT

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200 mg/m(2)) were alternated with a 3-week continuous infusion of FU (200 mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/economics , Conjunctivitis/chemically induced , Diarrhea/chemically induced , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Mitomycin/administration & dosage , Mouth Mucosa/drug effects , Mouth Mucosa/pathology , Nausea/chemically induced , Stomatitis/chemically induced , Survival Analysis , Treatment Outcome , Vomiting/chemically induced
20.
Ann Oncol ; 11(8): 1053-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11038045

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Genes, p53/genetics , Thymidylate Synthase/analysis , Tumor Suppressor Protein p53/biosynthesis , Adult , Aged , Colonic Neoplasms/immunology , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , Leucovorin/administration & dosage , Male , Middle Aged , Predictive Value of Tests , Thymidylate Synthase/metabolism
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