Tolerability Of Capecitabine Research Articles

Tolerability of capecitabine in difference racial/ethnic groups.

e18833 Background: Capecitabine (cap) is an oral chemotherapy agent used for treatment of solid malignancies. The recommended dose of cap generally ranges from 1000mg/m2 to 1250mg/m2 twice daily, but many patients require a dose reduction during treatment due to AE. It is unclear whether patients of different race have better tolerability of cap than others. In Asian populations for example, potential differences in tolerance have been attributed to low dietary folate intake. Race is a social construct; however it has been used to identify groups of patients within a population. We aimed to understand the tolerability of cap among patients of different racial/ethnic groups. Methods: In this retrospective chart review, we studied patients treated with cap at Tufts Medicine (three centers in MA, USA) between 2017-2021. Patients treated with cap alone, concurrent with other chemo, or concurrent with radiation for solid tumors were included. Patients were excluded if race/ethnicity data was not available. We collected demographic information, cap dose, AE, and dose reductions during the treatment period. Dose intensity (DI) was calculated (Total administered cap dose during treatment period (mg)/Recommended cap dose (mg/m2) * BSA (m2)). ANOVA was used to determine difference between groups. Results: 202 patients were included: 134 (66.3%) White, 35 (17.3%) Asian, 22 (10.9%) African American/Black, and 11 (5.4%) other race. 10 (5%) identified as Hispanic ethnicity. Most common cancer types treated were 46 (22.8%) breast, 44 (21.8%) colon, and 39 (19.3%) rectal. Average DI by race/ethnicity is outlined in Table 1. There was no statistically significant difference in DI among patients of different racial groups (p = 0.232). AEs leading to dose reduction or cap discontinuation occurred in 93 (46%) of patients, the most common outlined in Table 1. Conclusions: We found no significant difference in cap DI or toxicity among patients of different racial groups. The study is limited by the small sample size and that it is retrospective. The patients presented are racially diverse but live in one geographic area, which could impact environmental factors such as dietary folate intake. Our findings suggest that there is no difference in tolerated DI among all patients. Clinicians should not empirically reduce the dose of cap based on race and should assess tolerance on an individual basis. [Table: see text]

A study of the efficacy and tolerability of capecitabine and lobaplatin in advanced HER-2 negative breast cancer patients.

BackgroundThis study sought to examine the efficacy and adverse reactions of capecitabine and lobaplatin in the treatment of metastatic human epidermal growth factor receptor 2 (HER-2) negative breast cancer (BC).MethodsThis retrospective study examined 45 patients diagnosed with advanced HER-2 negative BC. Patients were enrolled in this study from November 2015 to June 2019. The patients received capecitabine and lobaplatin combination therapy. The therapeutic efficacy and side effects were evaluated after at least 2 cycles of treatment.ResultsTherapeutic efficacy and adverse reactions were evaluated in 38 patients, comprising 12 cases of partial response (PR), 19 cases of stable disease (SD), and 7 cases of progressive disease (PD). Among these, 3 patients required treatment delays or dose reductions for subsequent cycles, and 2 patients discontinued treatment. The overall response rate (ORR) was 31.58% and the disease control rate (DCR) was 81.58%. The ORR and DCR for hormone receptor positive, HER-2 negative (HR+/HER-2−) and triple negative breast cancer (TNBC) patients were 31.82% and 31.25%, and 86.36% and 75%, respectively. The median progression free survival (PFS) was 8 months, 6 months, and 6 months in patients receiving the therapeutics as a first-line, second-line, or third-line and beyond treatment, respectively. The main side effects were myelosuppression, including granulocytopenia, thrombocytopenia, and anemia. Among patients with grade 1 side effects or above, 28 patients (73.68%) had myelosuppression, and 13 patients (34.21%) had gastrointestinal reactions. Further, we investigated the association between side effects and clinical outcomes, and found that PFS was increased in patients with myelosuppression and gastrointestinal reactions.ConclusionsCapecitabine and lobaplatin combination therapy was effective and well tolerated among patients with advanced HER-2 negative BC.

106P Efficacy and tolerability of capecitabine and mitomycin-C based concurrent radiotherapy in patients with anal canal cancer

106P Efficacy and tolerability of capecitabine and mitomycin-C based concurrent radiotherapy in patients with anal canal cancer

Capecitabine therapy in recurrent/metastatic nasopharyngeal cancers.

e18515 Background: A wide range of chemotherapeutic agents have demonstrated antitumor activity in patients with recurrent or metastatic Nasopharyngeal Cancers (NPC). These therapeutic agents have different efficacy and toxicity profile. Capecitabine monotherapy had activity in recurrent/metastatic NPC based on small previous retrospective studies. The primary objective is to evaluate the overall response rate and tolerability of capecitabine in recurrent/metastatic NPC. Methods: A retrospective electronic chart review performed for 51 cases of recurrent/metastatic NPC patients who received capecitabine 1000-1,250 mg/m² twice daily two weeks on, one week off between 2011 to 2019 at King Faisal Specialist Hospital & Research Center (KFSH&RC). The Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 was used. Results: The median age at diagnosis was 42 years. 98% had a non-keratinized undifferentiated squamous cell carcinoma (Grade III). The most common sites for metastases were Bone (58.3%), Lung (50.0%), and liver (45.8%). 95% of patients received platinum-based chemotherapy and radiation therapy as the primary treatment. Capecitabine was used as the second or third line of treatment in the metastatic setting 45.1% and 43.1%, respectively. The patients tolerated the standard dose for a median of 6 cycles; only 20.0% of patients required a 25% dose reduction. The best response for capecitabine was complete response in 8 patients (15.7%), partial response in 14 patients (27.5%), stable disease in 10 patients, (19.6%), with a clinical benefit achieved in 32 patients (62.7%), and progressive disease in 16 patients (31.4%). The overall response rate to capecitabine was 43.2%, which was consistent regardless of the site of metastasis. The median progression-free survival was seven months (95%.CI: 5.3 -8.8). The one and three-year survival rates were 79% and 53%, respectively. Capecitabine was generally tolerated, the most common grade I & II adverse events were hand-foot syndrome (HFS) in 9 patients (20.5%), fatigue in 8 patients (15.7%), Diarrhea in 6 patients (11.7%), anemia in 5 patients (9.8 %), thrombocytopenia in 4 patients (7.8%) and neutropenia in 2 patients (4.0%). The most common grade III & IV was HFS in 3 patients (6%) and fatigue in one patient (2%) that led to treatment discontinuation after the first cycle. Conclusions: Capecitabine in Recurrent/Metastatic NPC is an effective and well-tolerated oral agent; however, a randomized prospective trial to evaluate capecitabine efficacy in this setting still recommended.

Abstract P6-18-30: Phase Ib/II study of capecitabine 7/7 schedule with neratinib in patients with HER2-positive metastatic breast cancer (MBC)

Abstract Background: Neratinib (N) is a potent irreversible inhibitor of HER1, HER2, and HER4 and has been shown to have antitumor activity in patients (pts) with human epidermal growth factor receptor 2 (HER2) - positive breast cancer. A previous study of combination of neratinib with capecitabine (X) was associated with > G 3 diarrhea in > 20% of patients. Currently, the NALA study is evaluating this combination of N with X at standard schedule against control. X at 7 day on and 7 day off schedule (7/7) has been shown to be well-tolerated with less ≥G3 toxicities. We are conducting a phase Ib/II study of N with X (7/7) in pts with pretreated HER2+ MBC (NCT03377387). Methods: Eligible pts had HER2+ MBC, normal left ventricular ejection fraction (LVEF ≥ 50%); pts can have any and up to 4 prior chemotherapy-based treatments in phase Ib and II portions, respectively. Primary endpoints are to define maximum tolerated dose and efficacy in phase I and phase II portions, respectively. Secondary endpoints include safety and tolerability; exploratory endpoint is to quantify cell-free DNA to correlate with response for phase II portion. There were 4 cohorts for phase Ib with dose level 1 with starting dose of X at 1500 mg BID at 7/7 schedule with N at 240 mg daily. Results: As of July 1, 2018 8 pts have been enrolled in 2 cohorts. The median age is 63y (range: 57-79), and median ECOG is 0 (range: 0-1). 4 patients were treated at dose level 1 and 2 of 4 patients experienced dose-limiting toxicity with G3 diarrhea during cycle 1. Other significant toxicities included G3 hand foot syndrome (n=1), G3 fatigue (n=1) and G3 nausea (n=1). Three pts have now been treated at dose level -1 (X at 1000 mg twice daily 7/7 and N at 240 mg daily) and no ≥ G3 toxicities has been noted. Once MTD is reached, the phase II portion will occur to assess the efficacy and to further establish the safety and tolerability of capecitabine and neratinib at the MTD. Conclusions: The phase Ib/II study combining neratinib and capecitabine 7/7 is ongoing and updated result will be presented. Citation Format: Wang R, Singh J, Sterlin V, Goldstein M, Lake D, Wong S, Baselga J, Norton L, Dang C. Phase Ib/II study of capecitabine 7/7 schedule with neratinib in patients with HER2-positive metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-30.

A phase I/II dose finding study evaluating the safety and tolerability of capecitabine and aflibercept in patients with unresectable metastatic colorectal cancer deemed unsuitable for doublet/triplet chemotherapy: results of the phase I study

A phase I/II dose finding study evaluating the safety and tolerability of capecitabine and aflibercept in patients with unresectable metastatic colorectal cancer deemed unsuitable for doublet/triplet chemotherapy: results of the phase I study

Quality of Life under Capecitabine (Xeloda®) in Patients with Metastatic Breast Cancer: Data from a German Non-Interventional Surveillance Study

Aim: This non-interventional surveillance study (NIS) collected data on the quality of life (QoL) of patients treated with capecitabine as mono- or combination chemotherapy in an outpatient setting. Methods: Capecitabine was administered orally for 14 days of each 21-day cycle. The main parameters of interest were QoL, compliance, patient and physician satisfaction, handling of hand-foot syndrome (HFS), and efficacy. The statistics were descriptive; some differences were compared using confidence intervals (CIs). Results: 735 patients from 161 centers received at least 1 dose of capecitabine. The median duration of observation was 5.5 months overall. The QoL global score was 53% (mean from the entire study population at all times), without any correlation to HFS. The overall response rate (ORR) was 35.1%, and the disease control rate (DCR) 64.4%. The median progression-free survival (PFS) was overall 6.81 months (95% CI 6.32-7.63 months) and it was significantly higher in patients with HFS (8.4 months, 95% CI 7.5-9.2 months, hazard ratio (HR) 0.60; p < 0.0001). The safety and tolerability of capecitabine were considered acceptable. The HFS incidence (all grades) was 27.1%. Conclusions: Capecitabine had a favorable risk-benefit relation in outpatient therapy. The QoL remained stable over the course of the investigation, indicating good compliance. HFS was a strong predictor of longer PFS and had no negative impact on the global QoL.

Tolerability of capecitabine in postoperative adjuvant chemotherapy in colon cancer: A single center study.

e14633 Background: According to Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial, capecitabine has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, w...

A phase II trial of frontline capecitabine and bevacizumab in poor performance status and/or elderly patients with metastatic colorectal cancer

This study aims to determine the efficacy and tolerability of capecitabine (CAP) plus bevacizumab (BEV) as treatment for frontline metastatic colorectal cancer (mCRC) in frail and/or elderly patients. This was an open label, multi-site, single arm, phase II study in frontline mCRC. In this study, patients (pts) who were frail (ECOG 2) or older patients with ECOG 1 performance status (PS) received CAP (1000 mg/m(2) bid, 14 days of every 21 days) plus BEV (7.5mg/kg iv once every 21 days). The primary objective was progression free survival (PFS). Secondary objectives were overall response rate (ORR) and toxicity. In terms of patients: 50 were enrolled; 5 withdrew consent prior to treatment; 45 were treated, and 41 were evaluable. The mean age was 75.9 (range 54-93) and 62% had an ECOG 2 PS. The median PFS was 6.87 months (95% CI, 5.1-11.5 months) and median overall survival was 12.7 months (95% CI, 6.9-12.7 months). The most common grades 3-4 toxicities were: diarrhea (17.8%), fatigue (13.3%), hand-foot syndrome (13.3%), dehydration (8.9%), hypertension (6.7%) and vomiting (6.7%). The results of this trial support the use of CAP plus BEV as first-line treatment for frail/elderly patients with metastatic CRC. The ORR (40%) is comparable to pooled data in elderly on fluorouracil (5-FU)+BEV. The median PFS (7.2 months) in this study is slightly lower than that seen with 5-FU+BEV but this study had a high percentage of ECOG PS 2 patients. Side effects were manageable with no new safety signals.

Effect of second-line treatment with capecitabine and thalidomide in patients with advanced pancreatic cancer

This study investigates the efficacy and tolerability of capecitabine plus thalidomide in patients with advanced pancreatic cancer who previously underwent gemcitabine-based therapy. Sixty-one patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen were enrolled. The patients were randomly divided into two groups. One group (31 patients) was treated with capecitabine alone, and another group was treated with capecitabine plus thalidomide. Capecitabine was administered orally twice a day at a dose of 1, 250 mg/m(2) for 14-day followed by 7-day rest and oral thalidomide 100 mg was given daily without interruption until disease progression or occurrence of unacceptable toxicity. The PFS was 2.8 months (95%CI 2.4 - 3.2) vs. 3.1 months (95%CI 2.6-3.6, P < 0.05) and the OS was 6.1 months (95%CI 5.3 - 6.9) vs. 6.3 months (95%CI 5.2 - 7.4, P = 0.426). In the capecitabine alone group, one patient experienced a partial response (PR), 10 patients showed stable disease (SD) and 20 patients had progressive disease (PD). The another group, two patients experienced a partial response (PR), 11 patients SD, and 17 patients PD. The disease control rates were 35.5% and 43.3%, respectively. The major adverse reaction in the two groups was grade 3 diarrhea. Capecitabine plus thalidomide regimen is marginally effective and well tolerated in the second-line setting in patients with gemcitabine-refractory advanced pancreatic cancer.

Efficacy and safety of capecitabine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma

The objective of this study was to evaluate the efficacy and tolerability of capecitabine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral capecitabine according to good clinical practice. Efficacy and safety outcomes were analyzed retrospectively. The response and adverse events rates and their exact confidence intervals (CIs) were calculated. Survival distributions were estimated using the Kaplan-Meier method. Twenty-nine patients were included in the study. Twenty-five patients (86%) had received at least three previous lines of chemotherapy. The disease control rate was 48% (95% CI: 29-67%). The median progression-free survival was 2.0 months (95% CI: 0.1-3.9 months) and the median overall survival was 7.0 months (95% CI: 4.1-9.9 months). Hand-foot syndrome, fatigue, and mucositis were the most frequent severe side effects. No patient died, and only three patients discontinued treatment because of side effects. Capecitabine seems to be an active and well-tolerated regimen, even in heavily pretreated, frail patients. 2C 'Outcomes Research'.

Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer

Our group applied mathematical modeling to capecitabine dosing and predicted 7 days of treatment followed by 7 days of rest (7-7) would improve efficacy and minimize toxicity. The conventional schedule of capecitabine limits full dosing in combination with other agents due to toxicity. Lapatinib inhibits the tyrosine kinase of HER2 and has activity when added to conventionally scheduled capecitabine for the treatment of patients with trastuzumab-refractory, HER2-positive, metastatic breast cancer (MBC). We performed this study to evaluate the activity and tolerability of capecitabine 7-7 with lapatinib in patients with trastuzumab-refractory MBC. Eligible patients had measurable, HER2-positive, MBC that progressed following exposure to trastuzumab. Treatment consisted of capecitabine 2,000 mg orally twice daily, 7-7 and lapatinib 1,250 mg orally daily. The primary endpoint was response rate. Secondary endpoints included toxicity, progression-free survival, and stable disease ≥ 6 months. Twenty-three patients were treated on study. More than 60% had prior chemotherapy for MBC and all had prior trastuzumab. After a median of 23 weeks (range 2-96+), five patients had partial responses (23; 95 CI, 7-44%) and six (27; 95 CI, 10-48%) had stable disease ≥ 6 months. Median progression-free survival was 9.4 months. The most common treatment-related toxicities ≥ grade (gr) 2 were hand-foot syndrome (gr 2 43%; gr 3 4% gr 4 0%), diarrhea (gr 2 26%; gr 3/4 0%), elevated liver chemistries (gr 2 17%; gr 3/4 0%), and anemia (gr 2 13%; gr 3 4%; gr 4 4%). No grade ≥ 3 nausea, vomiting, or diarrhea events occurred. This study demonstrated feasibility and after meeting biostatistical requirements for continued accrual was terminated in anticipation of slow enrollment. Capecitabine 7-7 with lapatinib was well tolerated with minimal gastrointestinal toxicity. Antitumor activity was observed in patients with trastuzumab-refractory MBC.

CAPECITABINE AND IRINOTECAN AS FIRST- LINE CHEMOTHERAPY FOR PATIENTS WITH METASTATIC COLORECTAL CANCER

RESUME: Objectives: Capecitabine is an oral fluoropyrimidine carbamate that is at least as effective than Fluorouracil / Leucovorin as first- line treatment for patients with metastatic colorectal cancer /CRC/. The topoisomerase I inhibitor Irinotecan has shown consistent efficacy in chemotherapynaive patients. The aim of this study was to determine the efficacy and tolerability of Capecitabine in combination with Irinotecan /XELIRI/ as first- line therapy in patients with advanced CRC. Methods: In the period 2007- 2009 twentyone consecutive patients with metastatic CRC entered the study. The treatment schedule consists of Capecitabine 1250 mg/m2 p.o. twice daily for 14 days with a 7- day rest period and intravenous Irinotecan 180mg/m2 day 1 with repetition of courses every 21 days. Results: Overall response rate was 33,3%. Median time to progression and overall survival was 7,6 months and 15,6 months, respectively. The most common grade 3- 4 adverse events were diarrhea and neutropenia. There were no treatment- related deaths. Conclusion: These results indicate that XELIRI is a potentially feasible and clinically active regimen in patients with advanced CRC.

Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment

Background:Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT.Methods:Patients aged 18–75 years, with Eastern Cooperative Oncology Group performance status 0–2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m−2 BID) was administered on days 1–14 every 21 days for at least two cycles.Results:A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1–9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%).Conclusions:Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules.

Phase II Trial of XELOX as First-Line Treatment for Patients with Advanced Gastric Cancer

Background: The prognosis of patients with advanced gastric cancer (AGC) remains poor, and no single chemotherapy regimen is recognized as a global standard. A phase II trial was conducted to determine the efficacy and tolerability of capecitabine and oxaliplatin (XELOX) given every 3 weeks in combination in patients with AGC. Methods: Patients with previously untreated AGC received intravenous oxaliplatin 130 mg/m² over 2 h on day 1 plus oral capecitabine 1,000 mg/m² twice daily on days 1–14, every 3 weeks. Treatment was continued for 8 cycles or until disease progression or intolerable toxicity. Results: Fifty patients were enrolled. In total, 210 cycles of XELOX were delivered. The OVERALL response rate was 42% (95% CI 28.6–56.7), with 2 complete and 19 partial responses. At 15.2 months of median follow-up, median time to progression and overall survival were 5.8 (95% CI 3.4–8.2) and 11.1 (95% CI 5.6–16.5) months, respectively. The most common hematological adverse event was neutropenia (56% of patients); grade 3–4 neutropenia was observed in 6 patients, with neutropenic fever in only 2 patients. The most common non-hematological toxicities were vomiting (34%), hand-foot syndrome (26%), diarrhea (24%) and neurosensory toxicity (22%). There were no treatment-related deaths. Conclusions: XELOX is active for the first-line treatment of AGC with a manageable tolerability profile.

Capecitabine in the Routine Treatment of Advanced Breast Cancer: Results from a Non-Interventional Observational Study in 876 Patients

Background: This observational study evaluated patient characteristics, treatment schedule and setting, efficacy and tolerability of capecitabine in routine clinical practice in Germany. Patients and Methods: Patients with advanced breast cancer pretreated with or ineligible for anthracycline-containing therapy were treated with capecitabine. Data were collected until disease progression or completion of 12 cycles (with long-term follow-up in progression-free patients). Results: 846 of the 876 patients enrolled between 2002 and 2007 were eligible. Capecitabine was administered as monotherapy in 64% (median starting dose 1,070 mg/m² bis in diem (b.i.d.)) and combination chemotherapy (typically with vinorelbine or docetaxel) in 36% (median starting dose 987 mg/m2 b.i.d.). Capecitabine was given as first-line therapy in 35% of patients. Objective response rate was 41% and median progression-free survival was 7.5 months. Good performance status at baseline was a significant predictor of efficacy. The most common non-hematological toxicity was hand-foot syndrome (all grades: 54%; grade 3: 7%). Myelosuppression and alopecia were substantially less common with capecitabine monotherapy than with capecitabine combination regimens. Conclusions: Capecitabine, alone or in combination, is a feasible, effective treatment for breast cancer. Our findings in real-life clinical practice compare favorably with results from interventional studies, perhaps reflecting the longer treatment duration possible at more tolerable doses.

Effect of combined oxaliplatin and capecitabine chemotherapy on advanced colorectal cancer

Objective To investigate the therapeutic effect and tolerability of capecitabine combined with oxaliplatin on advanced colorectal cancer. Methods Twenty patients with advanced colorectal cancer were treated with oxaliplatin 130mg/m2 intravenously once per week and capecitabine 1000mg/m2 orally twice daily for 14 days. Every 3 weeks was a treatment cycle. The effect was evaluated after two treatment cycles. Result Among 20 patients treated with oxaliplatin and capecitabine, complete response was 1 case and partial response was 7 eases. The total effective rate was 40.0%. Adverse effects were mainly grade Ⅰ～Ⅱ that includes marrow inhibitory, nausea and vomiting, diarrhea, mouth ulcer, peripheral neuritis and hand-foot syndrome. There was no serious chemo-therapy-related adverse effect. Conclusion The combined chemotherapy with oxaliplatin and capecitabine is an effective and better tolerance in treatment of advanced colorectal cancer and well worth clinical application. Key words: Advanced colorectal cancer; Capecitabine; Oxaliplatin; Combination chemotherapy

Phase II study of capecitabine as palliative treatment for patients (p) with squamous head and neck cancer (HNC) with locoregional and/or metastatic relapse after previous platinum-based treatment (PBT): Final results of Spanish Head and Neck Cancer Group (TTCC)

6047 Background: PBT is widely used as first line treatment in relapsed and/or metastatic HNC. Therefore, new non-platinum drugs need to be asses as second line treatment options. We proposed this study to evaluate activity and tolerability of capecitabine (X) when used as palliative monotherapy for relapsed HNC p previously treated with PBT. Methods: Forty patients (p) aged 18–75 years, ECOG PS 0–2, with advanced squamous HNC with locoregional and/or metastatic relapse previously treated with PBT and adequate bone marrow, renal and hepatic functions were included. X (1,250 mg/m2 BID) during 14 days was administered every 21 days, for at least 2 cycles. RECIST objective response rate (ORR) was assessed and toxicity following NCI-CTC v2 criteria. Results: Forty patients with median age 58 years old, all of them male, ECOG 0–2 (0:25%/1:70%/2:5%) and with squamous HNC, were analyzed. 34 p had local disease, 9 p regional disease and 19 p distant metastases(12 p lung). Median time since HNC diagnosis was 17.7 months and since disease extension diagnosis, 1.1 months. All p received a total of 169 cycles of X (median 4, range 1–9) and the median relative dose intensity was 91%. 7 p were not evaluable for response, since they do not receive at least 3 cycles ( 3 died, 2p due to toxicity, 2p due to decrease in ECOG PS ). ORR was 22.5 %.The median follow-up time was 5.2 months (alive p: 8.8 months), median TTP was 4.6 months and median OS was 6.2 months. Hematological toxicity G3/4 was reported in 6 p. 2p reported as grade 4 non-hematological toxicity: dysphagia and palmar-plantar erythrodysesthesia; grade III toxicities were: asthenia (4 p), anorexia (1 p), dehydratation (1 p), diarrhea (3 p), dysphagia (3 p) mucositis (4 p), weight loss (1 p), and palmar-plantar erythrodysesthesia (3 p). The most common grade II toxicity was asthenia (8 p). Conclusions: Capecitabine seems to be an active, feasible and well tolerated palliative treatment for advanced HNC patients that have previously received platinum-based schedules. No significant financial relationships to disclose.

Capecitabine and Trastuzumab in Heavily Pretreated Metastatic Breast Cancer

In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer, taxanes or vinorelbine plus trastuzumab are among the most widely applied options in the first-line setting. We evaluated the efficacy and tolerability of capecitabine plus trastuzumab after anthracycline and docetaxel or vinorelbine failure and prior trastuzumab exposure. Forty consecutive patients were included. Capecitabine was administered at a dose of 1,250 mg/m(2) bid for 14 consecutive days in 3-week cycles, with dose modifications if necessary. Trastuzumab was administered every 3 weeks. Time to progression (TTP) was defined as primary end point. Response was evaluated every 3 months using International Union Against Cancer criteria. TTP was a median of 8 months, and overall survival was 24 months. No significant difference was found for second-line and beyond second-line treatment. A complete response (CR) was observed in 2.5%, partial response (PR) in 17.5%, stable disease lasting at least 6 months (SD) in 50%, resulting in a clinical benefit rate (CR + PR + SD > or = 6 months) of 70%. Diarrhea (5%) and hand-foot syndrome (15%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Three patients (7.5%) developed brain metastases while receiving therapy. Capecitabine plus trastuzumab appears to be an effective and safe option in a heavily pretreated population. Therefore, a direct comparison of this regimen with capecitabine monotherapy in this setting is warranted.

Efficacy and Tolerability of Capecitabine with Weekly Paclitaxel for Patients with Metastatic Breast Cancer: A Phase II Report of the SAKK

Background: Paclitaxel and capecitabine have proven activity in the treatment of metastatic breast cancer (MBC). Paclitaxel increases the expression of thymidine phosphorylase, the enzyme that activates capecitabine. The purpose of this study was to evaluate the efficacy and tolerability of capecitabine in combination with weekly paclitaxel largely as first-line therapy in patients with MBC. Patients and Methods: From April 2002 to September 2004, 19 patients with MBC received oral capecitabine (1,000 mg/m² twice daily on days 1–14) plus i.v. paclitaxel (80 mg/m² on days 1, 8 and 15) in a 21-day cycle for a maximum of 6 cycles. Results: After a median follow-up of 19.3 months the overall response rate was 63% with 1 complete response (5%) and 11 partial responses (58%). Disease was stabilized in 1 patient (5%) and 3 patients had progressive disease (16%). Three patients were unable to be assessed for response to treatment. Median time to progression was 3.3 months, median time to treatment failure 3.0 months and median overall survival 13.8 months. A substantial number of patients experienced major side effects. The most common treatment-related adverse events were hand-foot syndrome (53%; grade 3: 37%), alopecia (42%; grade 3: 26%), diarrhea (32%; grade 3: 11%) and neurotoxicity (32%; grade 3: 16%). Hematologic toxicities were uncommon. Conclusion: The combination of capecitabine and paclitaxel appears to be active in MBC but the safety profile with the dosages used in this trial was unacceptably high and led to a short time to treatment failure. However, based on the efficacy data alternative schedules deserve further evaluation.