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E Bajetta

Publications and source records attributed to E Bajetta.

At least 19 recordsLinked to original sources
PubMed2006

Randomized phase II three-arm trial with three platinum-based doublets in metastatic non-small-cell lung cancer. An Italian Trials in Medical Oncology study.

BACKGROUND: Many patients with advanced non-small-cell lung cancer (NSCLC) do not tolerate cisplatin-based regimens because of its nonhemathological toxicity. PATIENTS AND METHODS: We evaluated the response rate safety of new platinum analogue regimens, randomizing 147 patients with nonoperable IIIB/IV NSCLC to (i) carboplatin (area under the curve = 5 mg min/ml) on day 1 plus gemcitabine (GEM) (1000 mg/m(2)) on days 1 and 8 for six cycles; (ii) same regimen for three cycles followed by docetaxel (Taxotere) (40 mg/m(2)) on days 1 and 8 plus GEM (1250 mg/m(2)) on days 1 and 8 for three cycles; (iii) oxaliplatin (130 mg/m(2)) on day 1 plus GEM (1250 mg/m(2)) on days 1 and 8 for six cycles. RESULTS: Intention-to-treat objective response rates were 25%, 25% and 30.6% in arms A, B and C, respectively. Median survival was 11.9, 9.2 and 11.3 months in arms A, B and C, respectively. Grade 3/4 neutropenia/anemia occurred in 29%/12.5%, 10%/16.5% and 8%/6% of arms A, B and C, respectively; grade 3/4 thrombocytopenia in 20.5%, 16.5% and 6%; grade 1/2 neurological toxicity in 43% of arm C. CONCLUSIONS: Oxaliplatin/GEM (arm C) had similar activity to carboplatin/GEM (arm A), but milder hematological toxicity and may be worth testing in a phase III study against carboplatin/GEM in patients not suitable for cisplatin. The sequential regimen gave no additional benefit.

Adult↗
PubMed2006

Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma.

BACKGROUND: The addition of cytokines to chemotherapy (CT) has obtained encouraging but contradictory results in metastatic melanoma. In this phase III trial, we compared the effects of CT [cisplatin, vindesine and dacarbazine (CVD)] with those of concurrent biochemotherapy (bioCT) consisting of CVD plus interleukin-2 and interferon-alpha2b. PATIENTS AND METHODS: A total of 151 untreated metastatic melanoma patients were randomized, 75 on arm A (cisplatin 30 mg/m2 on days 1-3, vindesine 2.5 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 1-3), and 76 on arm B (same CVD scheme plus interferon-alpha2b on days 1-5 and interleukin-2 on days 1-5 and 8-15, both administered subcutaneously), either recycled every 3 weeks. Response was assessed every two cycles. RESULTS: Ten percent of the patients were alive at a median of 52 months from start of therapy. We observed a response rate (RR) of 21% on arm A versus 33% on arm B; three patients (4%) given bioCT had complete responses (CRs). Median time to progression (TTP) was identical; median overall survival (OS) time was 12 months on arm A and 11 months on arm B. CONCLUSIONS: BioCT is not better than CT alone; the trend in favor of the bioCT in terms of RR did not translate into better TTP or OS. Therefore, bioCT cannot be recommended as standard first-line therapy for metastatic melanoma.

Adult↗
PubMed2006

Pathological features as predictors of recurrence after radical resection of gastric cancer.

BACKGROUND: The aim of this study was to investigate the pattern and timing of recurrence and to determine associated risk factors after radical resection of gastric cancer including D2 dissection. METHODS: A total of 274 patients who had undergone radical resection of gastric cancer with nodal involvement or T3-4 tumour were randomized to receive chemotherapy or no further treatment (control group). Locoregional recurrence and distant metastasis were analysed in a competing risks framework, by estimating the crude cumulative incidence in each group. Multiple regression models were used to investigate the influence of treatment and pathological features on the risk of recurrence. RESULTS: Overall, the 7 year rate of locoregional relapse was 15.8 per cent and that of distant recurrence was 34.5 per cent. There was a significant association between pathological node (pN) stage and distant relapse (P < 0.001), and between pathological tumour (pT) stage and locoregional recurrence (P = 0.024). Chemotherapy had no significant effect on either locoregional or distant recurrence. CONCLUSION: The rate of locoregional recurrence after radical surgery for gastric cancer was lower than that in studies based on more conservative surgery. The pT stage was related to the rate of locoregional recurrence whereas pN stage had an impact on distant recurrence.

Adult↗
PubMed2006

Capecitabine chemoradiation for rectal cancer after curative surgery.

This study reports the tolerability and feasibility of capecitabine, an oral fluoropyrimidine, chemoradiation as postoperative treatment. Stage II-III rectal cancer patients received 2 cycles of bolus 5-FU (425 mg/m2) and leucovorin (LV) (20 mg/m2) on days 1-5 q3w followed by oral capecitabine (800 mg/m2 bid) continuously during pelvic radiotherapy (total 50.4 Gy). Two additional cycles of 5-FU/LV were finally administered. Forty-one radically resected patients (median age: 61 years) were enrolled. All patients were evaluable for safety. Grade 3 adverse events included: proctitis (n = 3, 7%), diarrhea (n = 5, 12%), and leukopenia (n = 1, 2%). The overall rate of grade 3 diarrhea and leukopenia was 15% (95% confidence interval, 5-29%). Capecitabine chemoradiation in the adjuvant setting is well tolerated and is convenient to administer. These results support the use and further study of capecitabine chemoradiation in radically resected rectal cancer patients.

Adenocarcinoma↗
PubMed2005

Is the new WHO classification of neuroendocrine tumours useful for selecting an appropriate treatment?

BACKGROUND: Neuroendocrine tumours (NETs) are a rare and heterogeneous group of neoplasms. The most recent WHO classification provides clinical tools and indications to make the diagnosis and to suggest the correct treatment in different subgroups of patients. The aim of this trial was to apply the new classification criteria in clinical practice and, accordingly, to choose the most appropriate treatment. PATIENTS AND METHODS: Thirty-one evaluable patients, not previously treated, classified as advanced well differentiated NETs according to the new classification, were given long-acting release octreotide 30 mg every 28 days until evidence of disease progression. The treatment activity was evaluated according to objective, biochemical and symptomatic responses. Safety and tolerability were also assessed. RESULTS: Two partial objective tumour responses were obtained (6%), stabilization occurred in 16 patients (52%) and 95% of patients had a disease stabilisation lasting > or =6 months. However, eight patients showed rapid disease progression within 6 months of therapy and six patients after 6 months. Biochemical responses, evaluated by changes in serum chromogranine A levels were reported in 20/24 patients (83%). Symptomatic responses were observed in 6/14 patients (43%): a complete syndrome remission in one patient, partial syndrome remission in five patients, no change in four patients and progressive disease in four patients. The median overall survival was not reached, and the median time to disease progression was 18 months (range 1-49 months). The treatment was well tolerated, no severe adverse events were observed and no patient withdrew from the study because of adverse events. CONCLUSIONS: The WHO classification enables identification of low-grade NET patients who may be suitable for hormonal treatment. Octreotide LAR was seen to be effective in controlling the disease and was well tolerated. However, eight patients failed to respond to the treatment, despite histological evidence of a well differentiated tumour according to the new classification. This suggests that further histological examination should be carried out, especially in patients with visceral metastases and a short disease-free interval.

Adult↗
PubMed2005

Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.

Adult↗
PubMed2004

Complete remission of primary colon cancer in a metastatic patient treated with CPT-11 plus capecitabine.

BACKGROUND AND AIMS: The best treatment of patients with advanced colorectal cancer at the time of diagnosis is not well known, and the medical treatment is still unsatisfactory. CASE PRESENTATION: We report the case of a patient showing a complete remission of primary tumor after medical therapy with CPT-11 plus capecitabine. DISCUSSION: The best management of advanced disease at first presentation is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Osteoprotegerin and osteopontin serum values in postmenopausal advanced breast cancer patients treated with anastrozole.

Osteoprotegerin (OPG) is a potent antiresorptive molecule that binds NF-kappaB ligand, the final effector for osteoclastogenesis. OPG production is regulated by a number of cytokines and hormones. Osteopontin (OPN) is a secreted adhesive glycoprotein involved in tumour angiogenesis, and also a non-collagenous protein involved in bone turnover. OPN serum value is associated with tumour burden and survival in advanced breast cancer patients. The short-term effects of anastrozole on OPG and OPN serum values, and the usefulness of these analytes during follow-up were studied in 34 consecutive advanced breast cancer patients receiving anastrozole 1 mg/day. Blood samples were taken before treatment and at 2, 4, 8 and 12 weeks. OPG and OPN values were measured by ELISA. The results were analysed for all patients, and also separately for patients with (group A, 22 patients) and without (group B, 12 patients) bone metastasis. Whether the survival of all patients was related to their OPN serum values was also tested by placing patients into three groups (terciles) according to their baseline OPN values. No significant changes in OPG and OPN values were observed in the complete patient group. There was no difference in baseline OPG and OPN serum values between patients in groups A and B. In group A, a significant percentage increase in both OPG and OPN values from baseline was detected during treatment. No significant changes were reported for group B patients. Furthermore, in group A, a significant increase in both analytes was evident only for patients with progressive disease (PD). The Kaplan-Meier adjusted survival estimates for patients grouped according to tercile OPN values differed significantly (P = 0.001, log rank test). In conclusion, in the short term, anastrozole does not seem to affect OPG and OPN serum values in patients without bone disease. OPG and OPN appear to be useful predictors of the outcome of skeletal disease and elevated OPN values may be associated with short survival in advanced breast cancer patients.

Adult↗
PubMed2004

Position of nuclear medicine techniques in the diagnostic work-up of neuroendocrine tumors.

In recent years nuclear medicine has contributed to the impressive development of the knowledge of neuroendocrine tumors in terms of biology (receptor scintigraphy), pharmacology (development of new tracers), and therapy (radiometabolic therapy). At present, it is impossible to plan the management of a patient affected by a neuroendocrine tumor without performing nuclear medicine examinations. The contribution of nuclear medicine had affected and improved the management of these patients by offering various important options that are part of the modern diagnosis and treatment protocols. The clinical experience and the literature confirm that, among the wide variety of tracers and nuclear medicine modalities available today, metaiodobenzylguanidine (MIBG) and DTPA-D-Phe-octreotide (pentetreotide) are the radiopharmaceuticals of current clinical use. Several new somatostatin analogues are under investigation. Positron emission tomography (PET) supplies a range of labelled compounds to be used for the visualization of tumor biochemistry. In addition to the first routinely used PET tracer in oncology, 18F-labelled deoxyglucose (FDG), a number of radiopharmaceuticals based on different precursors such as fluorodopamine and 5-hydroxytryptophan (5-HTP) are going to gain a clinical role. Of course, the diagnosis of neuroendocrine tumors has to be based on integrated information derived from different examinations including nuclear medicine studies. The clinical presentation of neuroendocrine tumors is highly variable: sometimes they manifest typical or atypical symptoms but they may also be detected by chance during an X-ray or ultrasound examination carried out for other reasons. At disease presentation nuclear medicine modalities are sometimes able to direct physicians towards the clinical diagnosis thanks to the specificity of their imaging mechanisms. They also play a role in disease staging and restaging, patient follow-up and treatment monitoring. In addition, the biological characterisation of neuroendocrine tissues (receptor status, glucose metabolism, differentiation, etc.) allows the interpretation of radiopharmaceutical uptake as a prognostic parameter and sometimes as a predictor of the response to treatment.

Adrenal Gland Neoplasms↗
PubMed2003

Preclinical and clinical evaluation of four gemcitabine plus carboplatin schedules as front-line treatment for stage IV non-small-cell lung cancer.

BACKGROUND: To explore the activity and tolerability of gemcitabine (GEM) and carboplatin (CBDCA) in non-small-cell lung cancer (NSCLC) we tested four administration sequences on H460 NSCLC cells, and at the same time performed a randomized phase II trial using analogous schedules. PATIENTS AND METHODS: GEM was given first in two in vitro sequences, and CBDCA first in the other two; interaction was quantified calculating a combination index. Eighty-eight chemotherapy-naïve, stage IV NSCLC patients were randomly assigned to receive either: GEM (1000 mg/m(2)) on days 1 and 8 and CBDCA (AUC 5 mg.min/ml) on day 1, 4 h before GEM (arm A); same as arm A except CBDCA given 4 h after GEM (arm B); GEM on days 1 and 8 and CBDCA on day 2 (arm C); GEM on days 2 and 9 and CBDCA on day 1 (arm D). Courses were repeated every 21 days. RESULTS: In the preclinical study, CBDCA given before GEM produced a synergistic cytotoxic effect. Two complete and 29 partial responses occurred in 86 of 88 treated patients (intention-to-treat analysis 35%; 95% confidence interval 25.5% to 46.8%). One- and 2-year survivals were 44% and 11%, respectively. Grade 3/4 thrombocytopenia occurred in 11%; grade 3/4 neutropenia in 17%; and non-hematological toxicity was insignificant. Median survival was 11 months (range 7-18+), but better in patients receiving CBDCA first (arms A and D) (13 versus 9 months) than in patients receiving GEM first (arms B and C). The response was greater (50% versus 31%) in arm A than in the other arms. CONCLUSIONS: The CBDCA/GEM combination is safe and active against stage IV NSCLC. Our preclinical and clinical findings suggest that administration of CBDCA before GEM gives the better outcome.

Adult↗
PubMed2003

Phase II study of pemetrexed disodium (Alimta) administered with oral folic acid in patients with advanced gastric cancer.

BACKGROUND: The aim of this study was to assess the activity of pemetrexed in patients with advanced gastric cancer. PATIENTS AND METHODS: Thirty-eight eligible patients (median age 60 years) received pemetrexed 500 mg/m(2) every 3 weeks. Since toxicity was considerable in the first six patients, the protocol was amended to supplement subsequent patients with oral folic acid (5 mg/day on days -2 to +2 of every cycle). RESULTS: Among 36 stage IV patients evaluable for efficacy (six non-supplemented\30 supplemented), there were two complete and six partial responses. The response rate was 21% (95% confidence interval 8% to 32%) according to intention-to-treat analysis. All responding patients were in the supplemented group. The median duration of response was 4.6 months and the median survival was 7.8 months. Five of six non-supplemented patients (83%) developed grade 3/4 neutropenia; two (33%) unsupplemented patients discontinued; two (33%) patients died due to toxicity. In the supplemented group, 12 of 32 patients (37%) had grade 3/4 neutropenia. None of the supplemented patients discontinued treatment due to hematological toxicity. Severe non-hematological toxicities were infrequent. CONCLUSIONS: The activity of pemetrexed is promising in light of the tumor burden in these patients (all patients were stage IV and 39% had three or more organs involved). Toxicities were remarkably decreased with folic acid supplementation. Combination studies are warranted.

Adenocarcinoma↗
PubMed2002

Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.

Insulin-like growth factors (IGFs) play a fundamental role in cancer development by acting in both an endocrinal and paracrinal manner, and hormone breast cancer treatments affect the IGF system by modifying circulating growth factor levels. We evaluated total IGF-1, IGF-2, IGF binding protein (IGFBP)-1 and IGFBP-3 in the blood of 34 postmenopausal advanced breast cancer patients (median age 63 years, range 41-85) treated with anastrozole, a non-steroidal structure aromatase inhibitor (NSS-AI). The plasma samples were obtained at baseline, and after 2, 4, 8 and 12 weeks of treatment. The IGFs were quantitated by means of sensitive radioimmunoassays (RIAs). IGF-1 significantly increased during anastrozole treatment (baseline versus 12 weeks, P=0.031), IGF-2 showed a trend towards an increase, and IGFBP-1 constantly but not significantly decreased; IGFBP-3 did not seem to be affected at all. The anastrozole-induced changes in IGFs and IGFBP-1 appeared to be different in the patients receiving a clinical benefit from those observed in non-responders. We have previously shown that letrozole (a different type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the biological effects of anastrozole on the components of the IGF system confirm our previous observations.

Adult↗
PubMed2002

c-erbB 2 serum level as prognostic factor in hormonally treated advanced breast cancer patients.

To investigate whether c-erbB 2 serum levels may be predictive of clinical response, progression-free and overall survival in postmenopausal women with advanced breast cancer hormonally treated, 265 patients enrolled in previous clinical trials were evaluated. C-erbB 2 serum levels were assessed before the start of treatment and in a subgroup of patients also at the first response evaluation. In addition, serum CA 15.3 levels were determined. The role of c-erbB 2 was investigated by means of multiple regression models in which both c-erbB 2 and CA 15.3 values were modelled as continuous variables together with other known prognostic factors. The failure probability tended to be higher in the presence of high c-erbB 2 levels, but the trend was not statistically significant; in contrast, significant results were obtained for progression-free survival (PFS,P <0.001) and overall survival (OS, P=0.014). The within-patient c-erbB 2 variation significantly predicted PFS (P=0.006) and OS (P=0.040). It is worth noting that c-erbB 2 and CA 15.3 baseline levels were significantly correlated and that the prognostic effect of c-erbB 2 tended to disappear in the presence of high CA 15.3 levels for PFS and OS.

Journal Article↗
PubMed2002

Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group.

BACKGROUND: The aim of this study was to determine the efficacy of the EAP regimen (etoposide, adriamycin and cisplatin) followed by the Machover schedule (fluorouracil and folinic acid) given as adjuvant treatment to patients with poor prognostic factors (N+ or T3/4). PATIENTS AND METHODS: Before randomisation, the subjects were stratified on the basis of node involvement (N+ or N-) and the time from surgery to randomisation (< or = 21 days or > 22 days). The surgical procedures for sub-total or total gastrectomy with D2 dissection were standardised among the participating centres. RESULTS: Between December 1992 and December 1997, 274 patients were enrolled: 137 in the treatment arm and 137 in the control arm. The majority of the patients (90%) were N+. After a median follow up of 66 months (range 2-83), the 5-year overall survival (OS) was 52% in the treatment arm and 48% in the control arm [hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65-1.34]; the 5-year disease-free survival (DFS) was 49% and 44%, respectively (HR: 0.83; 95% CI 0.59-1.17). Among the patients with N-/N+ (1-6), the 5-year OS was 61% in the treatment group and 60% in the control group; in those with N+ (1-6), it was 42% and 22%. The treatment was completed by 87% of patients. Drug-related grade 3/4 WHO toxicities included leukopenia (21%), nausea and vomiting (14%), mucositis (9%), neutropenia (3%) and thrombocytopenia (2%). There were two deaths due to sepsis. CONCLUSIONS: Although our results are not statistically significant, there was a limited relative risk reduction in the patients receiving adjuvant therapy (17% in DFS and 7% in OS). The data suggest that D2 surgery may have a favourable impact on OS.

Adult↗
PubMed2002

Efficacy of a chemotherapy combination for the treatment of metastatic neuroendocrine tumours.

OBJECTIVES: Neuroendocrine tumours (NETs) are heterogeneous neoplasms for which there is no standard treatment. We have previously proposed an effective polychemotherapy (5-fluorouracil, dacarbazine and epirubicin), which only produced objective responses of brief duration. The present study aimed to assess in a multidisciplinary manner the efficacy of the same regimen at intensified doses in patients with advanced NETs. PATIENTS AND METHODS: Eighty-two consecutive patients entered the study, of whom 21 had inoperable, locally advanced disease and 61 had metastatic disease. Seventy-two patients were evaluated for objective, biochemical and subjective responses. Response rate, time to progression (TTP) and overall survival (OS) were evaluated based on histotype. RESULTS: An objective response was observed in 20 patients (intention-to-treat and standard analysis 24.4% and 27.8%, respectively). Complete biochemical and subjective responses were obtained in 25.1% and 38.9% of the cases. The median duration of treatment was 4 months and the objective responses had a median duration of 38 months. After a 60-month follow-up the median TTP and OS were 21 and 38 months, respectively. CONCLUSIONS: Our polychemotherapy regimen is effective, with long duration, and is well tolerated both for gastroenteropancreatic and lung NETs, as well as for tumours with a more aggressive clinical behaviour. The new WHO endocrine tumour histotyping, examining also the tumour biology, may give additional information for selecting patients to chemotherapy.

Adult↗
PubMed2002

Biological activity of anastrozole in postmenopausal patients with advanced breast cancer: effects on estrogens and bone metabolism.

BACKGROUND: To study the short-term biological effect of anastrozole on serum estrogens, androgens, 17-hydroxyprogesterone (17OH-PGR), gonadotrophins, sex hormone binding globulin (SHBG) and bone metabolism markers. MATERIALS AND METHODS: Thirty-four consecutive patients with advanced breast cancer received anastrozole 1 mg/day. Blood samples were taken before commencement of treatment and at 2, 4, 8 and 12 weeks during treatment to measure serum levels of estrogens (E(1), E(2) and E(1)-S), androgens [androstenedione (Delta(4)), dihydrotestosterone (DHT), testosterone (TST), free TST, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S)], 17OH-PGR, SHBG and gonadotrophins. As an indicator of bone resorption, we measured serum levels of C-terminal telopeptide of type I collagen (ICTP) and the cross-linked N-telopeptide of type I collagen (NTx), and for osteoblastic activity, intact osteocalcin (BGP) and bone alkaline phosphatase (BAP). RESULTS: After 2 weeks E(1 )and E(1)-S levels decreased on average by 56% (range 23.1-88.8%) and 75.8% (range 52.4-87.2%), respectively; E(2) decreased on average by 62% (range 31.4-89.6%). No significant changes were detected in levels of androgens or 17OH-PGR. There was a significant increase in gonadotrophins over time (P = 0.0001 for both luteinizing hormone and follicle-stimulating hormone), and a significant decrease in SHBG (P = 0.0001). A progressive significant increase in bone metabolism serum markers was detected in all patients: BAP, P = 0.039; BGP, P = 0.016; ICTP, P = 0.0021; and NTx, P = 0.0013. In particular, patients with bone metastases had a statistically significant increase of bone resorption markers (ICTP, P = 0.0019; NTx, P = 0.025) and borderline for bone formation markers. In patients without bone disease, BAP, BGP and ICTP remained unchanged, whereas serum NTx significantly increased (P = 0.019). CONCLUSIONS: Anastrozole is a selective aromatase inhibitor as it does not modify serum levels of androgens and 17OH-PGR. In our experience no relationship was found in the short-term period between serum estrogen suppression and bone metabolism.

Adult↗
PubMed2002

First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin.

PURPOSE: To evaluate the safety profile of capecitabine using data from a large, well-characterized population of patients with metastatic colorectal cancer treated in two phase II studies. In these trials, capecitabine achieved significantly superior response rates, equivalent time to disease progression and equivalent survival compared with 5-fluorouracil (5-FU)/leucovorin. PATIENTS AND METHODS: Patients (n = 1207) were randomized to either oral capecitabine (1250 mg/m2 twice daily, on days 1-14 every 21 days) or intravenous (i.v.) bolus 5-FU/leucovorin (Mayo Clinic regimen). RESULTS: Capecitabine demonstrated a safety profile superior to that of 5-FU/leucovorin, with a significantly lower incidence of diarrhea, stomatitis, nausea, alopecia and grade 3 or 4 neutropenia leading to significantly fewer neutropenic fever/sepsis cases and fewer hospitalizations. All patients in the capecitabine group received a starting dose of 1250 mg/m2 twice daily and the majority (66%) did not require dose modification for adverse events. In the 5-FU/leucovorin group, 58% of patients did not require dose reduction for toxicities. The capecitabine dose-modification scheme reduced the recurrence of key toxicities without compromising efficacy. In both treatment arms, patients with moderate renal impairment at baseline (estimated creatinine clearance 30-50 ml/min) experienced a higher incidence of grade 3 or 4 toxicities. This increase was more pronounced with 5-FU/leucovorin. CONCLUSIONS: Capecitabine is at least as effective, better tolerated and more convenient than i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer. Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events. The phase III data and an additional pharmacokinetic study support a lower starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30-50 ml/min) and a contra-indication in patients with severely impaired creatinine clearance at baseline (<30 ml/min). For patients with normal or mildly impaired renal function at baseline, the standard starting dose is well tolerated. The incidence and severity of adverse events in patients with moderate renal impairment at baseline who were treated with 5-FU/leucovorin was more pronounced, indicating that capecitabine provides a better-tolerated alternative.

Administration, Oral↗