Biomedical subjects

R Labianca

Publications and source records attributed to R Labianca.

At least 55 records · Page 3Linked to original sources

PubMed2001

A multinational study to measure the value that patients with cancer place on improved emesis control following cisplatin chemotherapy.

BACKGROUND: The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. OBJECTIVE: To measure the value that patients with cancer place on improved emesis control and quality of life. DESIGN: Willingness-to-pay analysis. SETTING: Five study sites in Canada, Italy, Spain and Greece. PATIENTS AND PARTICIPANTS: 245 patients with cancer either receiving chemotherapy with cisplatin or who had received cisplatin-based chemotherapy within the previous 6 months. METHODS: After background information had been presented, patients were asked to define the maximum that they would pay per day for a drug that reduced their risk of acute and delayed (days 2 to 5) emesis by 20 and 30%, respectively. Costs were converted to US dollars ($US) using year 2000 exchange rates. RESULTS: For a 20% improvement in acute emesis, Canadian, Italian and Spanish patients with cancer were willing to pay $US46, $US34 and $US63 per day, respectively, compared with $US8 for patients from Greece (p < 0.001). For a 30% improvement in delayed emesis, Canadian, Italian and Spanish patients with cancer were also willing to pay more than their Greek counterparts (SUS41, $US31, $US50 and $US9 daily for 4 days, respectively; p < 0.001). These significant differences in patient value between countries remained, even after adjusting for socioeconomic variables and previous history of emesis. CONCLUSIONS: There are substantial cultural differences in how patients with cancer value benefit and improved quality of life. Since the majority of the world's population resides outside North America and Western Europe, there may be a need to re-evaluate perceived levels of patient benefit and measures of quality of life.

Antiemetics↗

PubMed2000

Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente).

BACKGROUND: Several studies have investigated the possible role of the adjuvant chemotherapy after curative resection for gastric cancer failing to show a clear indication; previous meta-analyses suggested small survival benefit of adjuvant chemotherapy, but the statistical methods used were open to criticisms. MATERIALS AND METHODS: Randomised trials were identified by means of Medline and CancerLit and by selecting references from relevant articles. Systematic review of all randomised clinical trials of adjuvant chemotherapy for gastric cancer compared with surgery alone, published before January 2000, were considered. Pooling of data was performed using the fixed effect model. Death for any cause was the study endpoint. The hazard ratio and its 95% confidence intervals (95% CI), derived according to the method of Parmar, were the statistics chosen for summarising the relative benefit of chemotherapy versus control. RESULTS: Overall 20 articles (21 comparisons) were considered for analysis. Three studies used single agent chemotherapy, seven combination of 5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU without anthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82, 95% CI: 0.75-0.89, P < 0.001). Association of Anthracyclines to 5-FU did not show a statistically significant improvement when compared with the effect of the other regimens. CONCLUSIONS: Chemotherapy produces a small survival benefit in patients with curatively resected gastric cancer. However, taking into account the limitations of literature based meta-analyses, adjuvant chemotherapy is still to be considered as an investigational approach.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

A combination of a fixed dose rate infusion of gemcitabine associated to a bolus 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: Laboratory evidences suggest the possibility that an infusion rate of 10 mg/m2/min may be more effective than the standard 30-min infusion of Gemcitabine (GEM). PATIENTS AND METHODS: Thirty-four patients with histologically verified locally unresectable and/or metastatic pancreatic carcinoma received GEM at the dose of 1,500 mg/m2 with an infusion rate of 10 mg/m2/min, associated to 5-fluorouracil (5-FU) at the dose of 600 mg/m2. Both drugs were administered weekly for two consecutive weeks out of every three weeks. RESULTS: One complete and five partial responses have been observed for an overall response rate of 17% (95% CI: 3%-27%). The time to progression was 3.7 months with a median survival of 5.7 months. A clinical benefit was obtained in 5 of 29 patients (17%). Grade 3-4 WHO toxicities included neutropenia (35%) and thrombocytopenia (10%). CONCLUSION: It is unlikely that a fixed dose rate infusion of GEM, at least with this dose, can improve palliation in comparison with the standard 30-min infusion schedule in advanced pancreatic cancer.

Aged↗

PubMed2000

Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a randomized study. GISCAD, IOR and collaborating centers.

BACKGROUND: We have recently suggested that bolus 5-fluorouracil (5-FU) may work via a RNA directed mechanism while continuous infusion 5-FU may kill cells via a thymidylate synthase related pathway. It may thus be possible to selectively modulate each schedule biochemically. We have compared an alternating regimen of bolus and continuous infusion 5-FU, selectively modulated for the schedule of administration, with modulated bolus 5-FU in advanced colorectal cancer patients. PATIENTS AND METHODS: Two hundred fourteen patients from nineteen Italian centers were randomized to the control arm consisting of biweekly cycles of MTX, 200 mg/m2 on day 1, followed by bolus 5-FU 600 mg/m2 on day 2 and 6-S-leucovorin rescue, or to the experimental arm consisting of two biweekly cycles of the same regimen as in the control arm alternated to three weeks of continuous infusion 5-FU (200 mg/m2 day) + weekly bolus 6-S-leucovorin, 20 mg/m2. RESULTS: Nine CR and twenty-seven PR were obtained on one hundred eleven evaluable patients treated in experimental arm (RR = 32%, 95% confidence interval (95% CI): 24%-42%), while two CR and eleven PR were observed among one hundred three evaluable patients in control arm (RR = 13%, 95% CI: 7%-21%). WHO grade 3-4 toxicity occurred in 13% of cycles of experimental arm and in 8% of cycles in control arm. The PFS was significantly longer in experimental arm (6.2 vs. 4.3 months, odds ratio 0.66, P = 0.003), while the overall survival was similar in both arms (14.8 months in experimental arm vs. 14.1 months in control arm); quality of life was similar as well. Eighty percent of patients receiving second-line chemotherapy in control arm were treated with continuous infusion 5-FU. CONCLUSIONS: Alternating, schedule-specific biochemical modulation of FU is more active than MTX --> 5-FU as first-line treatment of advanced colorectal cancer. However, the overall survival was similar suggesting that alternating bolus and infusional 5-FU upfront may be as effective as giving them in sequence as first- and second-line treatment.

Adult↗

PubMed2000

Gemcitabine plus vinorelbine in elderly or unfit patients with non-small cell lung cancer.

Cisplatin-based combinations are efficacious in increasing the overall survival of patients with non-small cell lung cancer (NSCLC), but their toxicity makes them unsuitable for elderly and unfit patients. The primary objective of this non-randomized phase II study was to evaluate the feasibility and activity of the gemcitabine plus vinorelbine combination in previously untreated elderly and/or unfit patients with measurable stage III or IV NSCLC. Forty-three patients aged >/= 65 years or with contraindications against cisplatin treatment (36 males and seven females: median age 66 years; range 48-75: PS 0 = 11, PS 1 = 19, PS 2 = 13) received intravenous (i.v.) gemcitabine 1000 mg m(-2), followed by vinorelbine 25 mg m(-2)i.v. on day 1 and 8 every 21 days. Fifteen patients (34.9%) achieved partial remission (confidence interval: 27. 6-42.2%) for a median duration of 6 months; the median survival of these patients has not yet been reached. A further 15 had stable disease for a median of 4 months and a median survival of 7 months. The 10 patients (23.2%) who experienced disease progression had a median survival of 4 months. Three patients are not evaluable. The 1-year actuarial survival rate is 31.1%. The treatment was well tolerated: only 35% of the patients had grade 3 or 4 granulocytopenia on day 14, none experienced episodes of neutropenic fever, and there was no evidence of severe haematological toxicity upon recycling. Only 9% of the patients suffered from gastrointestinal toxicity (grade 3); increased but reversible transaminase levels were observed in 11.6%. In conclusion, the results of this phase II study show that the combination of gemcitabine and vinorelbine is active and well tolerated in NSCLC, and thus encourage its use in elderly or unfit patients.

Aged↗

PubMed1999

Patients' opinions, feelings, and attitudes after a campaign to promote the Di Bella therapy.

BACKGROUND: An emotional campaign promoting the Di Bella cancer therapy was launched by the Italian media in 1997. Its effects on patients' hopes, feelings, and decision-making processes were largely unknown. We undertook an investigation of this issue. METHODS: Between Feb 25 and March 31, 1998, a ten-item questionnaire was distributed to 1300 unselected adult patients attending 13 cancer centres throughout Italy. Four expert psycho-oncologists reviewed the design and validity of the contents of the questionnaire. Sociodemographic information was also collected. FINDINGS: 1120 (86%) questionnaires were returned and analysed. The main sources of information were television/radio (62%) and newspapers (26%); only 5% cited doctors. The campaign induced optimism in the patients about the efficacy of the method (ineffective 1%, effective 42%, uncertain 57%), and 53% said their hope of cure was increased. However, 48% felt more confused. 24% do not discuss new treatments with their oncologists, and 20% would like to but cannot. When choosing a treatment, the advice of a trusted doctor was judged more important than scientific progress (53% vs 32%) and 63% would try even unproven treatments in the hope of a cure. Replies to many of the questions were influenced by patients' educational attainment and by the degree of communication with their oncologists. INTERPRETATION: Science cannot prevent the harm caused by such campaigns and their psychological consequences, particularly for less educated patients. When making decisions, patients are looking for hope from the treatment and trust in their doctor, both of which depend on effective doctor-patient communications that therefore need to be improved.

Clinical Trials, Phase II as Topic↗

PubMed1999

A new palliative prognostic score: a first step for the staging of terminally ill cancer patients. Italian Multicenter and Study Group on Palliative Care.

In recent years, extensive research has been performed to identify prognostic factors that predict survival in terminally ill cancer patients. This study describes the construction of a simple prognostic score based on factors identified in a prospective multicenter study of 519 patients with a median survival of 32 days. An exponential multiple regression model was adopted to evaluate the joint effect of some clinico-biological variables on survival. From an initial model containing 36 variables, a final parsimonious model was obtained by means of a backward selection procedure. The Palliative Prognostic Score (PaP Score) is based on the final model and includes the following variables: Clinical Prediction of Survival (CPS), Karnofsky Performance Status (KPS), anorexia, dyspnea, total white blood count (WBC) and lymphocyte percentage. A numerical score was given to each variable, based on the relative weight of the independent prognostic significance shown by each single category in the multivariate analysis. The sum of the single scores gives the overall PaP Score for each patient and was used to subdivide the study population into three groups, each with a different probability of survival at 30 days: (1) group A: probability of survival at 30 days > 70%, with patient score < or = 5.5; (2) group B: probability of survival at 30 days 30-70%, with patient score 5.6-11.0; and (3) group C: probability of survival at 30 days < 30%, with patient score > 11.0. Using this method, 178/519 (34.3%) patients were classified in risk group A, 205 (39.5%) patients were in risk group B, and 136 (26.2%) patients were in risk group C. The patients classified in the three risk groups had a very different survival experience (logrank = 294.8, P < 0.001), with a median survival of 64 days for group A, 32 days for group B, and 11 days for group C. The PaP Score based on simple clinical and biohumoral variables proved to be statistically significant in a multivariate analysis. The score is valid in this population (training set). An independent validation on another patient series (testing set) is required and is the object of a companion paper.

Algorithms↗

PubMed1999

Successful validation of the palliative prognostic score in terminally ill cancer patients. Italian Multicenter Study Group on Palliative Care.

The aim of this work was to validate a previously constructed prognostic score for terminally ill cancer patients in order to determine its value in clinical practice. The Palliative Prognostic Score (PaP Score) was tested on a population of 451 evaluable patients consecutively entered in the hospice programs of 14 Italian Palliative Care Centers. The score subdivided patients into three specific risk classes based on the following six predictive factors of death: dyspnea, anorexia, Karnofsky Performance Status (KPS), Clinical Prediction of Survival (CPS), total white blood count (WBC), and lymphocyte percentage. The performance of the PaP Score index in the training and testing sets was evaluated by comparing mortality rates in the 3 prognostic risk categories. The score was able to subdivide the validation-independent case series into three risk groups. Median survival was 76 days in group A (with a 86.6% probability of 30-day survival), 32 days in group B (with a 51.6% probability of 30-day survival), and 14 days in group C (with a 16.9% probability of 30-day survival). Survival medians were remarkably similar to those of the training set (64 days in group A, 32 days in group B, and 11 days in group C). In the complex process of staging terminally ill patients, the PaP Score is a simple instrument which permits a more accurate quantification of expected survival. It has been validated on an independent case series and is thus suitable for use in clinical practice.

Algorithms↗

PubMed1999

A phase II study of Tomudex alternated with methotrexate, 5-fluorouracil, leucovorin in first-line chemotherapy of metastatic colorectal cancer.

PURPOSE: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of tomudex with methotrexate (MTX)/5-fluorouracil (5-FU)/leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven metastatic colorectal cancer and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values, and no prior chemotherapy, were selected. Treatment was tomudex 3 mg/m2 and, after two weeks, MTX, 200 mg/m2 by 30' infusion after hydration with 1500 ml saline solution, followed on day 2 by 5-FU, 600 mg/m2 and leucovorin, orally, 15 mg for six times every 6 hours, beginning 24 hours after MTX. Cycles were repeated every four weeks. Tumor response assessment was performed after three cycles. RESULTS: Thirty-four patients were enrolled in this study, of whom twenty-four had liver metastases, nine local relapse, five lymph node involvement, four lung metastases, and three peritoneal carcinomatosis. Four patients achieved objective responses (one complete and three partial), for an overall response rate of 12% (95% CI: 0%-22%). Twelve patients had stable disease and 18 progressed on therapy. Median survival for all patients was 13 months. Two patients experienced grade 3 WHO neutropenia while hepatotoxicity was reported in 13 patients (6 grade 1, 3 grade 2, 3 grade 3, 1 grade 4), suggesting that this combination could increase hepatic toxicity in comparison to tomudex or MTX/5-FU alone. CONCLUSIONS: Our results suggest that this regimen does not warrant further investigation in advanced colorectal cancer patients, at least not with this schedule and doses.

Adenocarcinoma↗

PubMed1999

Intensive weekly chemotherapy is not effective in advanced pancreatic cancer patients: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

Twenty-two patients, with locally advanced unresectable and/or metastatic pancreatic carcinoma, received weekly administration of cisplatin 40 mg m(-2), 5-fluorouracil 500 mg m(-2), epidoxorubicin 35 mg m(-2), 6S stereoisomer of leucovorin 250 mg m(-2) and glutathione 1.5 mg m(-2), supported by a daily administration of lenograstim at a dose of 5 microg kg(-1). Nineteen patients were men and three were women. Median age was 63 years (range 47-70). At study entry, pain was present in 15 out of 22 patients (68%) with a mean value of Scott-Huskisson scale of 27.6+/-23.8, whereas a weight loss >10% was present in 15 patients. After eight weekly treatments, three partial responses were achieved for a response rate of 13% (95% CI 0-26%), five patients had stable disease and 14 progressed on therapy. Pain was present in 9 out of 22 patients (40%) with a mean value of Scott-Huskisson scale of 12.3+/-18.4. Eight patients (36%) (three partial response and five stable disease) had a positive weight change. Toxicity was mild: WHO grade III or IV toxicity was recorded in terms of anaemia in 7 out of 188 cycles (3.7%), of neutropenia in 9 out of 188 cycles (4.7%) and of thrombocytopenia in 3 out of 188 cycles (1.5%). Median survival of all patients was 6 months. The outcome of this intensive chemotherapy regimen does not support its use in pancreatic cancer.

Aged↗

PubMed1999

A combination of gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

In a randomized clinical trial, gemcitabine (GEM) was more effective than 5-fluorouracil (5-FU) in advanced pancreatic cancer patients. GEM and 5-FU have different mechanisms of action and their combination, from a theoretical point of view, could result in a higher activity. To test activity and feasibility of such a combination, a multi-institutional phase II study was initiated in November 1996 by the Italian Group for the study of Digestive Tract Cancer (GISCAD). Primary objectives of this study were to determine the activity in terms of response rate and clinical benefit, while the secondary objective was toxicity. According to the optimal two-stage phase II design, 54 patients were enrolled. Schedule was: GEM 1000 mg m(-2) intravenous (i.v.), and 5-FU 600 mg m(-2) bolus i.v. weekly for 3 weeks out of every 4. All the 54 patients were symptomatic (pain, weight loss, dyspepsia). A clinical benefit was obtained in 28 patients (51%) (95% confidence interval (CI) 38-64%). Two patients achieved a partial response and 34 a stable disease. Median survival for all the patients was 7 months. Side-effects were mild: no gastrointestinal or haematological grade 3-4 toxicity (WHO) were recorded. We observed only six episodes of grade 2 (WHO) leukopenia and seven episodes of thrombocytopenia. Although the non-randomized design of this study suggests caution in the interpretation of these data, in consideration of the low incidence of toxicity and the favourable results obtained in terms of clinical benefit, it may be worthwhile to test more active schedules of 5-FU (continuous infusion) in combination with gemcitabine.

Adult↗

PubMed1999

Subcutaneous administration of interleukin-2 and interferon-alpha 2b in advanced renal cell carcinoma: long-term results.

Clinical data have supported the combination of subcutaneous r-interleukin-2 (rIL-2) and r-interferon-alpha (rIFN-alpha) as a promising combination for advanced renal cell carcinoma (RCC), with a reduced toxicity. We evaluated the activity and safety of this outpatient immunotherapy and report on the clinical results and the long-term survival analysis. Objective responses was observed in 9 of 50 (18%) patients, 6 of whom (12%) achieved a complete response. Overall median survival is 12 months, six patients were surviving at a median follow-up of 24 months, and three (6%) are still progression-free.

Adult↗

PubMed1999

Which 5-fluorouracil regimen?--the great debate.

5-Fluorouracil (5-FU) has been available for over 40 years and has been used in a wide variety of different regimens for the treatment of advanced colorectal cancer, a malignancy with a poor prognosis that is common in industrialized countries. However, despite numerous clinical trials in which 5-FU has been used alone and in combination with a variety of modulating agents [chiefly leucovorin (LV)], and has been administered by bolus injection and i.v. infusion, the optimal regimen for the management of advanced colorectal cancer remains unclear, and there are notable national and international variations in clinical practice. The toxicity of 5-FU also remains an obstacle to the achievement of overall clinical benefit in many patients. The introduction of novel chemotherapeutic agents may make it necessary to reassess the place of 5-FU in the treatment of advanced colorectal cancer. This article debates these issues with a review of clinical trials of 5-FU, and concludes that the future lies in the utilization of novel and established agents in combinations that may significantly improve outcomes, rather than in continuing experimentation with various schedules of 5-FU and LV.

Antimetabolites, Antineoplastic↗

PubMed1999

Evolution of physicians' attitudes towards practice guidelines.

OBJECTIVES: To assess changes in physicians' attitudes towards practice guidelines and towards the role of empirical evidence in their development. METHODS: The findings from two surveys carried out in 1993 and 1997 on the same random sample from two Italian medical specialty societies were compared. In both studies, physicians were mailed a questionnaire asking their views on the goals and role of practice guidelines in influencing clinical decision-making, and the role of empirical evidence versus subjective clinical experience in their development. RESULTS: One hundred and seventy physicians participated in both surveys. An increasing proportion of physicians accepted that cost containment could be a legitimate goal of practice guidelines (from 26% in 1993 to 40% in 1997; P = 0.010). More clinicians (43% in 1993 and 57% in 1997; P < 0.01) supported the use of empirical evidence, as opposed to subjective clinical experience, as the primary basis for practice guidelines. Although only a tiny minority of physicians (6% in 1993 and 1997) supported the view that practice guidelines should reflect patient preferences, an increased proportion of physicians supported the participation of representatives from outside the medical profession in their development. The level of support increased from 6% in 1993 to 26% in 1997 (P < 0.001) in the case of consumers, from 24% to 38% (P = 0.015) for patient involvement and from 16% to 33% (P = 0.003) in the case of health care administrators. CONCLUSIONS: The documented changes suggest that more clinicians acknowledge the role of empirical evidence and the need for a dialogue with other professionals and patient groups in the development of practice guidelines than was the case in the recent past.

Adult↗

PubMed1998

Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer.

BACKGROUND: In phase II trials, irinotecan is active in patients with advanced colorectal cancer, but the survival and clinical benefit of irinotecan compared with second-line fluorouracil by continuous infusion is not known. METHODS: 267 patients who had failed to respond to first-line fluorouracil, or whose disease had progressed after treatment with first-line fluorouracil were randomly allocated irinotecan 300-350 mg/m2 infused once every 3 weeks or fluorouracil by continuous infusion. Treatment was given until disease progression, unacceptable toxic effects, or the patient refused to continue treatment. The primary endpoint was survival, while progression-free survival, response rate, symptom-free survival, adverse events, and quality of life (QoL) were secondary endpoints. FINDINGS: 133 patients were randomly allocated irinotecan and 134 were allocated fluorouracil by continuous infusion. Patients treated with irinotecan lived for significantly longer than patients on fluorouracil (p=0.035). Survival at 1 year was increased from 32% in the fluorouracil group to 45% in the irinotecan group. Median survival was 10.8 months in the irinotecan group and 8.5 months in the fluorouracil group. Median progression-free survival was longer with irinotecan (4.2 vs 2.9 months for irinotecan vs fluorouracil, respectively; p=0.030). The median pain-free survival was 10.3 months and 8.5 months (p=0.06) for irinotecan and fluorouracil, respectively. Both treatments were equally well tolerated. QoL was similar in both groups. INTERPRETATION: Compared with fluorouracil by continuous infusion second-line irinotecan significantly improved survival in patients with advanced colorectal cancer.

Adenocarcinoma↗

PubMed1998

Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research.

BACKGROUND: There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days). METHODS: 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control). The patients were followed up for a median of 63 months, with yearly screening for recurrent disease. The primary endpoint was survival; analyses were by intention to treat. FINDINGS: 619 patients in the control group and 616 in the PVI group met eligibility criteria. 164 (26%) control-group patients and 173 (28%) PVI-group patients died. 5-year survival did not differ significantly between the groups (73 vs 72%; 95% Cl for difference -6 to 4). The control and PVI groups were also similar in terms of disease-free survival at 5 years (67 vs 65%) and the number of patients with liver metastases (79 vs 77%). INTERPRETATION: PVI of fluorouracil, at a dose of 500 mg/m2 for 7 days, cannot be recommended as the sole adjuvant treatment for high-risk colorectal cancer after complete surgical excision. However, these results cannot eliminate a small benefit when PVI is used at a higher dosage or in combination with mitomycin.

Aged↗

PubMed1998

GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.

BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. METHODS: The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. CONCLUSIONS: Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated, effective 6-month adjuvant regimen for patients with colon carcinoma that has no detrimental effect on their quality of life.

Adult↗

PubMed1998

Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study.

BACKGROUND: Oxaliplatin is a new cytotoxic agent from the diaminocyclohexane family with proven antitumor activity against colon cancer cell lines. Activity in patients with colorectal carcinoma previously treated with 5-fluorouracil has been studied in three single-agent phase II trials, showing a reproducible response rate of 10%. Here we report a phase II trial with oxaliplatin as a first-line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Twenty-five patients were entered in the study. All of them had metastatic disease without previous chemotherapy, and at least one lesion had to be measurable by computed tomography (CT). Therapy consisted of a two-hour infusion of oxaliplatin at a dose of 130 mg/m2 every 21 days. RESULTS: The overall response rate determined by investigators was 20% (95% CI, 6.8%-40.7%). Eight patients (32%) had stable disease. The median time to disease progression in responders was six months (range four to nine). The median progression-free survival was four months and median overall survival 14.5 months (95% CI, 10-20 months). The main toxic effects were peripheral neuropathy (92%) and laryngopharyngeal dysesthesia (75%). No severe grade 3-4 neurotoxicities (NCI-CTC) were found. Gastrointestinal and hematological toxicities were mild. CONCLUSIONS: Oxaliplatin is an active agent in first-line chemotherapy for advanced colorectal cancer. It was well tolerated, caused no toxic deaths, had low hematotoxicity, well controlled gastrointestinal toxicity, and frequent but mild peripheral neurological symptoms. Therefore, it is of interest to associate oxaliplatin with other active compounds.

Adenocarcinoma↗