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Biomedical subjects

R Labianca

Publications and source records attributed to R Labianca.

At least 37 records · Page 2Linked to original sources
PubMed2003

Quality of life evaluation in a randomised trial of chemotherapy versus bio-chemotherapy in advanced melanoma patients.

This study analyses the health related quality of life (HRQOL) of advanced melanoma patients, in a randomised trial comparing bio-chemotherapy (bio-CT) versus chemotherapy (CT). The trial enrolled 178 patients and the median survival was not statistically different between the two arms. HRQOL was assessed at baseline and before each cycle of therapy, using the Rotterdam Symptom Checklist (RSCL) questionnaire completed with 140 patients. At baseline, overall quality of life and psychological distress scores were the most impaired, compared with the normal population. During treatment, the difference between the two arms in the changes from baseline was statistically significant (P=0.03) only in the overall quality of life score, with a decrease of 6.28 points in the bio-CT arm. The mean values decreased significantly in all domains in bio-CT arm, but only in activity level and physical symptom distress scores in the CT arm. Testing HRQOL variables and prognostic clinical factors in a Cox model, only the serum level of lactic dehydrogenase, baseline overall quality of life and the physical symptom distress scores remained significant independent prognostic factors for survival. A score of less than 75 points in the overall quality of life and in the physical symptom distress domains was associated with a Hazard Ratio (HR) of 2.31 (95% Confidence Interval (CI): 1.09-4.90) and 1.92 (95% CI: 1.10-3.36), respectively.

Adult↗
PubMed2003

Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma.

We measured the levels of the vascular endothelial growth factor (VEGF), matrix metalloproteinases type 2 and type 9 (MMP-2 and MMP-9) and tissue inhibitors of matrix metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the plasma of patients with ovarian carcinoma (n=40), in other gynaecological pathologies (n=30) and in the plasma of healthy volunteers (n=26). MMP-2 and MMP-9 (pro and active forms) gelatinolytic activity was measured by zymography. Enzyme-linked immunosorbent assays (ELISA) were used to assay soluble VEGF and TIMPs. Preoperative plasma VEGF levels were significantly higher in patients with ovarian cancer than in healthy volunteers (P<0.0001) or patients with a benign gynaecological pathology (P<0.0001). The expression of pro-MMP-9 was higher in the plasma of ovarian cancer patients than in the plasma of women with non-malignant disease (P=0.01) or healthy women (P<0.0002). Pro-MMP-2 was detected in the plasma of ovarian cancer patients, but levels did not differ from those in non-malignant disease or healthy donor samples. Plasma TIMP-1 and TIMP-2 levels were significantly higher in patients with ovarian carcinomas than in healthy volunteers (P<0.0001 and P=0.006, respectively) or in the patients with a non-malignant pathology (P<0.0001 and P=0.002, respectively). Sub-group analysis showed that VEGF and pro-MMP-9 were higher in the plasma of patients with serous carcinomas than other histological types. Furthermore, plasma VEGF and pro-MMP-9 levels were higher in the plasma of cancer patients with thrombocytosis. Throughout the study, and in the univariate analysis, no correlation was found between the VEGF, MMP and TIMP levels. Only TIMP-1 was associated with a poor survival and mortality risk.

Adult↗
PubMed2003

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: This phase II study was initiated to determine the activity and toxicity of a combination of gemcitabine (GEM) and cisplatin (CDDP) in patients with pancreatic cancer. PATIENTS AND METHODS: CDDP 35 mg/m(2) was given as a 30-min infusion and GEM 1000 mg/m(2) as a 30-min infusion. Both drugs were administered once weekly for 2 consecutive weeks out of every 3 weeks to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Forty-five advanced pancreatic cancer patients received this regimen for a total of 180 cycles of chemotherapy. One complete and four partial responses have been observed for an overall response rate of 9% (95% confidence interval 10% to 11%). Twenty-one patients (46%) had stable disease and 19 progressed on therapy. The median time to progression was 3.6 months, with a median survival of 5.6 months. A clinical benefit was obtained in nine of 37 patients (24%). Side-effects were mainly represented by hematological toxicity. Grade 3/4 WHO toxicities included neutropenia (6% of the patients) and thrombocytopenia (11%). The dose of GEM and CDDP was reduced in 14 patients (31%) and treatment was delayed in 10 patients (22%). CONCLUSIONS: Our results in terms of response rate, clinical benefit and survival do not support an advantage for the combination of GEM and CDDP given by this schedule.

Adult↗
PubMed2003

Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron.

BACKGROUND: Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron. PATIENTS AND METHODS: In this multicenter, randomized, double-blind, stratified, phase III study, 570 adult cancer patients were randomized to receive a single i.v. dose of palonosetron 0.25 mg, palonosetron 0.75 mg or ondansetron 32 mg, each administered 30 min before initiation of moderately emetogenic chemotherapy. The primary end point was the proportion of patients with no emetic episodes and no rescue medication [complete response (CR)] during the 24 h after chemotherapy administration (acute period). Secondary end points included efficacy in treatment of delayed CINV (</=5 days post-chemotherapy) and overall tolerability. RESULTS: 563 patients were evaluable for efficacy. CR rates were significantly higher (P <0.01) for palonosetron 0.25 mg than ondansetron during the acute (0-24 h) (81.0% versus 68.6%, respectively), delayed (24-120 h) (74.1% versus 55.1%) and overall (0-120 h) (69.3% versus 50.3%) periods. CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals. Both treatments were well tolerated. CONCLUSIONS: A single i.v. dose of palonosetron 0.25 mg was significantly superior to i.v. ondansetron 32 mg in the prevention of acute and delayed CINV.

Adult↗
PubMed2003

Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors.

In patients with stage III colorectal cancer (CRC) who have undergone potentially curative resection, adjuvant treatment with 6 months' of 5-fluorouracil (5-FU) plus folinic acid (FA) is generally accepted as standard treatment and leads to a 5% to 10% improvement in absolute survival when compared with a no-chemotherapy control. In stage II CRC, the benefit of adjuvant chemotherapy has yet to be established. In metastatic CRC, randomized trials of irinotecan have consistently demonstrated that use of the drug, either alone or in combination with 5-FU/FA, prolongs survival. To investigate whether this benefit can be extended to patients with earlier disease, a series of multicenter trials are randomizing stage III colon cancer patients to adjuvant 5-FU/FA regimens with or without the addition of irinotecan. The role of adjuvant irinotecan is also being assessed in stage II colon cancer and in patients with rectal tumors. The risk/benefit ratio of adjuvant therapy in both stage III and stage II disease would be decreased if patients at the highest risk of relapse could be identified. Data from retrospective analyses suggest that DNA indexes, angiogenesis and some genetic/biological markers (loss of heterozygosity at chromosome 18 and the presence of microsatellite instability) identify prognostic differences in colon cancer patients. Their value as a guide to the intensity of adjuvant therapy required should be tested by randomized trial, as should the use of markers such as thymidilate synthase overexpression as a means of tailoring drug choice to tumor characteristics.

Antineoplastic Combined Chemotherapy Protocols↗
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

Adjuvant treatment of colorectal cancer (current expert opinion derived from the Third International Conference: Perspectives in Colorectal Cancer, Dublin, 2001).

This article summarises the progress that has been made in the adjuvant treatment of colorectal cancer over the last decade. In view of the consequent improvements in recurrence rates and in overall survival, the development of effective adjuvant treatments for colorectal cancer is considered as one of the most important to be made in clinical oncology over the last decade. Treatment recommendations based on evidence-based data and on expert opinions are summarised in this manuscript. However, a consensus cannot be reached on all aspects of treatment because of data that is currently emerging that will influence clinical practice and because of the many ongoing clinical trials. Those involved in the treatment of colorectal cancer should therefore be encouraged to continue to provide optimal patient care and to participate in well designed clinical trials in order to increase the evidence upon which they can base their clinical judgements and in order to make further progress.

Antineoplastic Agents↗
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

Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype.

BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for primary colorectal carcinoma, were prospectively studied for K-ras mutations by PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon 12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon 13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph-node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate analysis showed that codon 13 K-ras mutations, but not any mutation, were independently related to risk of relapse or death. CONCLUSIONS: Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.

Adenocarcinoma↗
PubMed2001

A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients.

BACKGROUND: Adjuvant chemotherapy is standard treatment for patients with resected colon cancer who are at high risk for recurrence, but the efficacy and toxicity of such treatment in patients more than 70 years of age are controversial. METHODS: We performed a pooled analysis, based on the intention to treat, of individual patient data from seven phase 3 randomized trials (involving 3351 patients) in which the effects of postoperative fluorouracil plus leucovorin (five trials) or fluorouracil plus levamisole (two trials) were compared with the effects of surgery alone in patients with stage II or III colon cancer. The patients were grouped into four age categories of equal size, and analyses were repeated with 10-year age ranges (< or =50, 51 to 60, 61 to 70, and >70 years), with the same conclusions. The toxic effects measured in all trials were nausea or vomiting, diarrhea, stomatitis, and leukopenia. Patients in the fluorouracil-plus-leucovorin and fluorouracil-plus-levamisole groups were combined for the efficacy analysis but kept separate for toxicity analyses. RESULTS: Adjuvant treatment had a significant positive effect on both overall survival and time to tumor recurrence (P<0.001 for each, with hazard ratios of death and recurrence of 0.76 [95 percent confidence interval, 0.68 to 0.85] and 0.68 [95 percent confidence interval, 0.60 to 0.76], respectively). The five-year overall survival was 71 percent for those who received adjuvant therapy, as compared with 64 percent for those untreated. No significant interaction was observed between age and the efficacy of treatment. The incidence of toxic effects was not increased among the elderly (age >70 years), except for leukopenia in one study. CONCLUSIONS: Selected elderly patients with colon cancer can receive the same benefit from fluorouracil-based adjuvant therapy as their younger counterparts, without a significant increase in toxic effects.

Adenocarcinoma↗
PubMed2001

5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer.

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.

Adult↗
PubMed2001

Adjuvant treatment of colorectal cancer at the turn of the century: European and US perspectives.

BACKGROUND: Despite early scepticism, several studies of systemic adjuvant 5-fluorouracil (5-FU)-based chemotherapy demonstrated significant benefits in high-risk colon cancer. As many clinical investigations have since been conducted in this setting, a comprehensive literature review was undertaken to clarify the role of adjuvant therapy in the treatment of colorectal cancer. DESIGN: Current and future adjuvant treatment approaches in colorectal cancer were reviewed, and differences in the present-day North American and European practices were highlighted. RESULTS AND CONCLUSIONS: 5-FU plus leucovorin for six months is generally considered the 'standard' adjuvant treatment in Dukes' stage C (stage II) colon cancer. Large-scale international trials of other strategies are required to provide further advances in treatment outcome. Following the lead of the USA Intergroup trials, a recently initiated cooperative effort, the Pan-European Trials in Adjuvant Colon Cancer (PETACC), may serve as a European model for such investigations. In T3 and/or lymph-node positive rectal cancer, postoperative (chemo)radiotherapy in the USA is considered the adjuvant treatment of choice. However, most European investigators have advocated for preoperative intensive short-course irradiation instead. Randomized trials in this area are ongoing. In the near future, new drugs for the treatment of colorectal cancer may lead to tailored therapies.

Antimetabolites, Antineoplastic↗
PubMed2001

New drugs and combinations in the palliative treatment of colon and rectal cancer.

Colorectal cancer (CRC) is a common disease. The overall survival has improved only marginally in recent decades despite advances in surgery and early detection. Potentially curative resection at disease presentation can be performed only in 70-80% of the patients, and overall survival at 5 years is less than 60%. Advanced disease is associated with a poor prognosis. Treatment for advanced colorectal cancer has nevertheless made progress in the last few years. Systemic chemotherapy doubles the survival of these patients compared to untreated controls. Chemotherapy has demonstrated effective palliation, improvement of quality of life (QoL) and symptom improvement in such patients. For nearly four decades, fluorouracil (5FU) has been the mainstay of treatment. New compounds active against colorectal cancer are now available. Several studies on this topic are ongoing.

Administration, Oral↗
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

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

Treatment of classical Kaposi's sarcoma with gemcitabine.

BACKGROUND: Several drugs are active in aggressive classical Kaposi's sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of deoxycytidine with cytotoxic activity in the treatment of solid tumours, has been found to have no serious side-effects. OBJECTIVE: To evaluate the usefulness of treating patients affected by aggressive CKS with gemcytabine. METHODS: Twelve patients with a recurrent aggressive form of CKS previously treated with chemotherapy were treated with gemcitabine. The drug was administered intravenously at the dose of 1.2 g/week for 2 weeks, followed by a 1-week interval, until maximal response was reached. Objective responses and toxicity were evaluated according to WHO criteria. RESULTS: Eleven evaluable patients achieved an objective response: CR in 1/11 and PR in 10/11. Toxicity was limited. CONCLUSION: This study shows the usefulness of treating patients affected with aggressive CKS with gemcitabine, in order to obtain control of the disease and to reduce the related symptoms as well as to overcome a possible resistance to previous treatments.

Aged↗