Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS.

PURPOSE: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. METHODS: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. RESULTS: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. CONCLUSIONS: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable.

Seom guidelines for the treatment of gastric cancer 2015.

Gastric cancer is the fourth cause of death by cancer in Spain and a significant medical problem. Molecular biology results evidence that gastroesophageal junction tumors and gastric cancer should be considered as two independent entities with a different prognosis and treatment approach. Endoscopic resection in very early tumors is feasible. Neoadjuvant and adjuvant therapy in locally advanced resectable tumor increase overall survival and should be considered standard treatments. In stage IV tumors, platinum-fluoropyrimidine-based schedule, with trastuzumab in HER2-overexpressed tumors, is the first-line treatment. Different therapies in second line have demonstrated in randomized studies their clear benefit in survival improvement.

First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study.

BACKGROUND: Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC. METHODS: Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg(-1) and oxaliplatin 130 mg m(-2) on day 1, plus capecitabine 1000 mg m(-2) bid orally on days 1-14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP). RESULTS: The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%). CONCLUSIONS: Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.

The role of plasma IDO activity as a diagnostic marker of patients with colorectal cancer.

High levels of indoleamine 2,3-dioxygenase (IDO) are involved in tumour escape mechanisms. The aim of this study is the evaluation of L-kynurenine of plasma as marker of diagnostic and prognostic in patients with colorectal cancer. The study included 78 patients with colorectal cancer, of whom 15 % were in stage I/II, 30 % in stage III, and 55 % in stage IV, and was compared with a control group of 70 healthy subjects. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.917, with a specificity of 100 % and with a sensitivity to detect cancer of the colon of 85.2 %, taking 1.83 µM as a cut-off point. The overall survival analysis also indicated that patients with low levels of L-kynurenine in plasma increased survival rate after 45 months of follow-up (P = 0.032). These results show that the plasma levels of L-kynurenine could be a good biomarker to differentiate individuals with colorectal cancer from healthy individuals.

A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable, nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN). This randomized, open-label, phase III clinical trial compared the efficacy between standard CCRT and two different induction chemotherapy (ICT) regimens followed by CCRT. PATIENTS AND METHODS: Patients with untreated LASCCHN were randomly assigned to ICT (three cycles), with either docetaxel (Taxotere), cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CCRT [7 weeks of radiotherapy (RT) with cisplatin 100 mg/m(2) on days 1, 22 and 43]; or 7 weeks of CCRT alone. The primary end points were progression-free survival (PFS) and time-to-treatment failure (TTF). RESULTS: In the intention-to-treat (ITT) population (n = 439), the median PFS times were 14.6 (95% CI, 11.6-20.4), 14.3 (95% CI, 11.8-19.3) and 13.8 months (95% CI, 11.0-17.5) at TPF-CCRT, PF-CCRT and CCRT arms, respectively (log-rank P = 0.56). The median TTF were 7.9 (95% CI, 5.9-11.8), 7.9 (95% CI, 6.5-11.8) and 8.2 months (95% CI, 6.7-12.6) for TPF-CCRT, PF-CCRT and CCRT alone, respectively (log-rank P = 0.90). There were no statistically significant differences for overall survival (OS). Toxic effects from ICT-CCRT were manageable. CONCLUSION: Overall, this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN.

Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study.

BACKGROUND: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. METHODS: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). RESULTS: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). CONCLUSION: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.

Cancer chemotherapy reduces plasma total polyphenols and total antioxidants capacity in colorectal cancer patients.

Our aim was to investigate the effect of chemotherapy on plasma total antioxidant capacity and polyphenols in patients with colon cancer. Plasma samples were collected from 70 CRC patients under chemotherapy treatment, and 15 non-treated patients. The control group included 71 healthy individuals. Plasma ABTS and FRAP were measured as biomarkers of antioxidant total capacity and the total phenols as an indicator to determine the polyphenols levels in plasma. Treatment with chemotherapy protocols resulted in a significant decrease of ABTS (-24 %, p < 0.048), FRAP (-15 %, p < 0.046) and polyphenols (-46 %, p < 0.05) compared with the values of those not treated. The total antioxidant capacity was significantly lower (-18 % for ABTS and -12 % for FRAP) in patients with metastasis as compared with patients without metastasis. The plasma total phenols, were also decreased (-16 %, p = 0.005) in metastasis patients. The patients with colorectal cancer have decreased total antioxidant capacity and the values are lower in patients treated with chemotherapy. Furthermore, CEA tumor marker levels are associated with a lower plasma total antioxidant capacity, and therefore with the progress and development of the disease.

Lynch syndrome diagnostics: decision-making process for germ-line testing.

Cancer risks and medical management of Lynch syndrome (LS) differ from other hereditary or familial clustering of colorectal cancer. Differential diagnosis has improved as a result of the growing clinical and molecular knowledge about LS. Appropriate application of these advances in several scenarios constitutes a decision-making process to further decide germ-line testing with accuracy and efficiency. However, an only molecular-screening algorithm, with a limited number of steps and choices, may be difficult to devise. How, when, where and at what expense to use the different diagnostic tools remain dynamic and changeable under different circumstances. From a clinical point of view, it is advisable to discuss conflicting aspects to guide LS diagnosis.

Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer.

BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance

Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients.

BACKGROUND: North American and Japanese non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activation via tyrosine kinase (TK) mutations respond dramatically to gefitinib treatment. To date, however, the frequency and effect of EGFR TK mutations have not been examined in European patients. PATIENTS AND METHODS: Eighty-three Spanish advanced NSCLC patients who had progressed after chemotherapy, were treated with compassionate use of gefitinib. Patients were selected on the basis of available tumor tissue. Tumor genomic DNA was retrieved from paraffin-embedded tissue obtained by laser capture microdissection. EGFR mutations in exons 19 and 21 were examined by direct sequencing. RESULTS: EGFR mutations were found in 10 of 83 (12%) of patients. All mutations were found in adenocarcinomas, more frequently in females (P=0.007) and non-smokers (P=0.01). Response was observed in 60% of patients with mutations and 8.8% of patients with wild-type EGFR (P=0.001). Time to progression for patients with mutations was 12.3 months, compared with 3.6 months for patients with wild-type EGFR (P=0.002). Median survival was 13 months for patients with mutations and 4.9 months for those with wild-type EGFR (P=0.02). CONCLUSIONS: EGFR TK mutational analysis is a novel predictive test for selecting lung adenocarcinoma patients for targeted therapy with EGFR TK inhibitors.

Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer.

The purpose of this study was to evaluate the efficacy, assessed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1, followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days 2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1-12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.

[Capecitabine: an oral chemotherapeutic agent against metastatic breast and colorectal cancer]. / Capecitabina: un quimioterápico oral en la lucha contra el cáncer de mama y colorrectal metastásico.

Capecitabine is the first drug in a new fluoropyrimidine class that offers distinct characteristics. On one hand its oral administration mimics continuous fluorouracil infusion while remaining convenient with higher patient acceptance and compliance rates and avoiding intravenous administration-associated complications and financial costs. On other hand it provides intra-tumour selective activation, thus potentially facilitating local management and therefore improved anti-tumour activity as well as reduced systemic toxicity. The concentration of thymidine phosphorylase an enzyme essential for capecitabine activation in tumour cells increases after exposure to cytotoxics such as taxanes, cyclophosphamide, gemcitabine or vinorelbine, which results in synergistic activity. It has been tried both as monotherapy and in combination with other chemotherapy agentsâboth in first-line regimes and in previously treated patients against metastatic colorectal and breast cancer, results being very good in terms of efficacy and tolerability.

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer.

PURPOSE: To evaluate the efficacy and tolerability of paclitaxel, carboplatin and etoposide when administered in combination to previously-untreated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients (n=95) with limited-stage disease (LSD; n=45) or extensive-stage disease (ESD; n=50) from 14 Spanish hospitals were entered into the study. Etoposide was administered 80 mg/m(2)/day intravenous (i.v.) on days 1, 2 and 3, paclitaxel 175 mg/m(2) i.v. on day 3 and carboplatin area-under-the-concentration-time-curve=6; i.v. on day 3, of a 3-week cycle, and repeated for up to 6 cycles. RESULTS: The overall response (OR) rate was 74% (n=70; 32 complete, 38 partial). Although the OR in LSD and ESD patients was similar (73 vs 74%, respectively), the percentage complete response was significantly higher among the former (49 vs 20%). The main toxicities were grade 3-4 neutropenia and febrile neutropenia (62 and 18%, respectively) and there were 3 toxic deaths. Other toxicities were rare or easily manageable. Disease-free survival and overall survival rates at 1 year were 53 and 70% in LSD and 18 and 39% in ESD patients, respectively. CONCLUSION: The results indicate that the combination of paclitaxel, etoposide and carboplatin has an anti-tumour activity in SCLC that is comparable to other combination regimens, and is well tolerated.

Raltitrexed in the treatment of elderly patients with advanced colorectal cancer: an active and low toxicity regimen.

In spite of the high prevalence of advanced colorectal cancer in the elderly, we have little data on the efficacy and toxicity of chemotherapy in this age group. Raltitrexed is a thymidylate synthetase inhibitor with known activity in the treatment of advanced colorectal cancer. The objective of this study was to analyse the efficacy and tolerance of raltitrexed in elderly patients with advanced colorectal cancer. 92 patients diagnosed with advanced colorectal cancer aged >or=70 years were entered into the study. Raltitrexed was given at a dose of 3 mg/m(2) once every 3 weeks for a minimum of three cycles. A total of 511 cycles were given with a median of five cycles per patient. 20 out of the 90 patients evaluable for response achieved a partial response (PR) (22%, 95% Confidence Interval (CI): 17-36%), 43 (48%) remained stable and 27 showed progression (30%). The mean duration of response was 24 weeks and the progression-free interval was 15 weeks. The overall median survival was 41 weeks. 31 patients (39%, 95% CI: 28-50%) experienced a clinical benefit (improvement of the performance status without a worsening of symptoms or relief of symptoms without a worsening of the performance status). The main toxicities were gastrointestinal and haematological. 12 patients (13%) developed grade 3-4 side-effects: 7 had nausea/vomiting (8%), 6 a transaminase increase (7%), 4 asthenia (4%), 3 diarrhoea (3%), 2 neutropenia (2%), 2 anaemia (2%) and 1 thrombocytopenia (1%). Three toxic deaths occurred (3%). The group of patients with a creatinine clearance

Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group.

BACKGROUND: The authors designed this randomized, controlled trial to assess whether dose intensification of a cisplatin-etoposide combination (PE), achieved by shortening the interval between chemotherapy cycles, would improve response rate and survival. The maximum tolerated dose of PE was administered in either 3- or 4-week cycles to patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: One hundred twenty-three patients were randomized into two groups. The dose-intense arm received cisplatin 35 mg/m2 and etoposide 200 mg/m2 on Days 1-3 every 4 weeks. The dose-dense arm received the same schedule every 3 weeks along with 5 microg/kg of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) administered subcutaneously on Days 4-13. RESULTS: Patient characteristics were well balanced in both treatment arms. Fifty-four percent of patients were classified as Stage IIIB. A 32% increase in relative dose intensity was achieved in the dose-dense arm compared with the dose-intense arm. The response rates were 32% in the dose-intense arm and 27% in the dose-dense arm (P = 0.9). The median overall survival was higher in the dose-dense arm, 9 versus 7.2 months (P = 0.2). The main toxicity was myelosuppression, although the administration of GM-CSF significantly reduced the percentage of patients with Grade 4 granulocytopenia (53% vs. 78%). Fifty-four percent of the patients in the dose-intense arm and 35% of those in the dose-dense arm developed febrile neutropenia (P = 0.07). There were ten (8%) treatment-related deaths, three (4%) in the dose-intense arm and seven (12%) in the dose-dense arm (P = 0.3); three deaths in each arm were due to febrile neutropenia. CONCLUSIONS: The dose-intensification achieved in the dose-dense PE regimen did not correlate with significant improvements in response rate or survival and cannot be recommended in the light of the diversity of new drug combinations available today. However, the use of rhGM-CSF significantly reduced the incidence of severe granulocytopenia.

Granisetron plus methylprednisolone for the control of high-dose cisplatin-induced emesis.

This double-blind, double-dummy, randomized study compared the 24 h efficacy and safety of granisetron alone (3 mg i.v. over 30 s) or in combination with methylprednisolone (250 mg i.v. twice daily) in preventing nausea and vomiting in 308 patients (254 males) receiving high-dose cisplatin (100 mg/m2 or above) for mainly lung, and head and neck cancers. All patients received oral follow-on therapy comprising oral granisetron and methylprednisolone during the following 6 days. Primary efficacy variables were the proportions of complete responses (CR; no vomiting, no worse than mild nausea, no rescue and no withdrawal), no vomiting and no nausea over the first 24 h following initiation of the cisplatin infusion. The two treatment groups were well matched for demographics, cancer site, cisplatin dose and duration of infusion. Granisetron plus methylprednisolone was significantly more effective than granisetron alone for all primary efficacy variables: CR 78 versus 59% (p<0.001), no vomiting 80 versus 61% (p<0.001) and no nausea 74 versus 57% (p<0.002). Significantly more patients receiving the combination were free of any emetic symptoms (74 versus 54%, p<0.001). Significantly fewer patients receiving combination therapy also required rescue therapy with i.v. granisetron (12.2 versus 21.7%, p=0.026). During the follow-on period, complete response rates varied day by day from 50 to 71%. Both treatments were well tolerated, with constipation, abdominal pain and headache as the most frequent adverse events.

Uracil and tegafur modulated with leucovorin: an effective regimen with low toxicity for the treatment of colorectal carcinoma in the elderly. Oncopaz Cooperative Group.

BACKGROUND: In spite of the high prevalence of cancer in the elderly, little information is available about the efficacy and toxicity of chemotherapy in elderly patients. In a previous study, the authors demonstrated that the combination of uracil and tegafur (UFT) with leucovorin (LV) was active and well tolerated in patients with advanced colorectal carcinoma (ACC). The objective of the current study was to determine the efficacy and toxicity of this regimen in elderly patients with ACC. METHODS: Thirty-eight unselected patients older than 70 years (median age, 74 years) with measurable ACC were included. All patients were evaluable for toxicity and response. The regimen consisted of intravenous LV 500 mg/m2 on Day 1, oral LV 15 mg every 12 hours on Days 2-14, and oral UFT 390 mg/m2 on Days 1-14. Treatment was repeated every 28 days for a minimum of 4 courses per patient. RESULTS: Two hundred eighty-eight cycles of chemotherapy were delivered (median, 7 per patient). Two patients (5%) achieved a complete response and 9 (24%) a partial response, for an overall response rate of 29%. Toxicity was mild, without dose-limiting myelosuppression. Four patients (10%) experienced Grade 3-4 diarrhea, 1 patient had Grade 3-4 nausea/vomiting, and 1 had Grade 3-4 mucositis. Grade 3-4 toxicity was more frequent among women than men (38% vs. 4%, P < 0.05). CONCLUSIONS: Treatment with oral UFT modulated with LV is effective, well tolerated, and feasible on an outpatient basis for elderly patients with ACC. However, elderly women should be followed closely for the early detection of toxicity.