OBJECTIVEThe purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).

METHODSFour hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model.

RESULTSA total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea.

CONCLUSIONSThe genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Chemoradiotherapy, Adjuvant ; adverse effects ; Cyclin D1 ; genetics ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Diarrhea ; chemically induced ; etiology ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Polymorphism, Single Nucleotide ; Postoperative Period ; Prospective Studies ; Rectal Neoplasms ; genetics ; pathology ; surgery ; therapy ; Risk Factors

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Adult ; Aged ; Aged, 80 and over ; Anorexia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/pathology ; Diarrhea/chemically induced ; Disease-Free Survival ; Fatigue/chemically induced ; Female ; Hand-Foot Syndrome/etiology ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*drug therapy/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Invasiveness ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Portal Vein/*pathology ; Proportional Hazards Models ; Tomography, Spiral Computed ; Venous Thrombosis/*drug therapy/pathology

Diarrhea is a common adverse event of docetaxel with 20%-40% of incidence and severe diarrhea occurs in 5%-6%. Several treatment guidelines for chemotherapy induced diarrhea (CID) exist, however the prophylaxis for that is not well known. We describe a new prophylactic approach for the CID with loperamide. A 72-yr-old male patient with stage IV non-small-cell lung cancer developed diarrhea repeatedly after docetaxel-cisplatin chemotherapy. His diarrhea persisted despite treatment including loperamide and fasting. However, the diarrhea was successfully prevented when loperamide was given before and after the chemotherapy. To our knowledge, this is the first report of prophylactic approach for the CID with loperamide.
Aged ; Carcinoma, Non-Small-Cell Lung/*drug therapy/radiography ; Cisplatin/therapeutic use ; Diarrhea/chemically induced/*etiology ; Drug Therapy, Combination ; Humans ; Loperamide/*adverse effects/therapeutic use ; Lung Neoplasms/*drug therapy/radiography ; Male ; Neoplasm Staging ; Taxoids/*adverse effects/therapeutic use ; Tomography, X-Ray Computed

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Capecitabine ; Class I Phosphatidylinositol 3-Kinases ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease Progression ; Disease-Free Survival ; Exanthema ; chemically induced ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Hand-Foot Syndrome ; etiology ; Humans ; Middle Aged ; Mutation ; Neoplasm Staging ; Phosphatidylinositol 3-Kinases ; genetics ; Quinazolines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction

OBJECTIVETo observe the local control rate, survival time and side effect of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma.

METHODSForty patients with postoperative recurrent rectal carcinoma received three-dimensional conformal radiation therapy, 1.8 - 2.0 Gy/once, 5 times every week and the total dose was 54 - 65 Gy. At the same time, the patients took Tegafur orally 40 mg/m(2) twice per day for consecutive 28 days, and one cycle lasted for 42 days. The chemotherapy was applied for 2 cycles after radiotherapy.

RESULTSThe total effective rate (CR + PR) was 70.0%, improvement rate was 90.0%, 1-year survival rate was 70.0%, and 1-year local control rate was 62.5%. There was only a little side effect.

CONCLUSIONSThree-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma have definite effect, with a high local control rate, and patients well tolerance the treatment without serious side effect. It can apparently improve the life quality of the patients.

Adenocarcinoma ; drug therapy ; radiotherapy ; surgery ; Adult ; Aged ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Combined Modality Therapy ; Diarrhea ; etiology ; Exanthema ; chemically induced ; etiology ; Female ; Humans ; Leukopenia ; etiology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Postoperative Period ; Quality of Life ; Radiotherapy, Conformal ; adverse effects ; Rectal Neoplasms ; drug therapy ; radiotherapy ; surgery ; Remission Induction ; Survival Rate ; Tegafur ; adverse effects ; therapeutic use

OBJECTIVETo evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.

METHODSThree hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.

RESULTSAmong the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01).

CONCLUSIONSThe capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

Adult ; Agranulocytosis ; chemically induced ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Diarrhea ; chemically induced ; Disease Progression ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Hand-Foot Syndrome ; etiology ; Humans ; Leukopenia ; chemically induced ; Maintenance Chemotherapy ; Middle Aged ; Neoplasm Staging ; Remission Induction ; Retrospective Studies ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives

BACKGROUND AND OBJECTIVEConcurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and standard therapy in recent years. Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50%. This study aimed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma.

METHODSA total of 156 patients with stage IIa-IIIb cervical squamous cell carcinoma were randomly divided into the concurrent chemoradiotherapy group (experimental group) and radiotherapy group (control group). Intracavity and external beam radiation therapy were administered. At point A, 40-48 Gy were given by 10-12 fractions; at point B, 46-50 Gy were given by 23-25 fractions. In the same time, experimental group was treated by cisplatin (DDP, 40 mg) on day 1, repeated every week. Ten days after radiation therapy, TP regimen was administered as adjuvant chemotherapy.

RESULTSFor the experimental and control groups, the objective response rates were 88.61% and 75.32%, 1-year survival rates were 88.57% and 70.77%, 1-year local control rates were 81.43% and 64.62%, 3-year survival rates were 82.14% and 57.69%, and 3-year local control rates were 75.00% and 46.15%, with significant differences (P<0.05). Quality of life of all patients were significantly improved after treatment (P<0.05).

CONCLUSIONConcurrent chemoradiotherapy plus adjuvant chemotherapy for advanced cervical cancer can improve short-term and long-term survival and local control rates of patients, improve the quality of life, and the toxicity can be tolerated.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; pathology ; therapy ; Chemoradiotherapy ; adverse effects ; Chemotherapy, Adjuvant ; Cisplatin ; adverse effects ; therapeutic use ; Diarrhea ; chemically induced ; etiology ; Dose Fractionation ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; Quality of Life ; Remission Induction ; Survival Rate ; Taxoids ; adverse effects ; therapeutic use ; Uterine Cervical Neoplasms ; pathology ; therapy ; Vomiting ; chemically induced ; etiology

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is closely related with a wide range of gastrointestinal disease. One-week triple therapy is currently considered as the golden standard for the treatment of H. pylori infection. However, gastrointestinal abnormal responses are major pitfalls in such regimen. The aim of this study was to identify symptoms, frequency and severity of antibiotics-associated gastrointestinal abnormal responses during H. pylori eradication therapy. METHODS: Sixty-seven patients with H. pylori infection between September 2005 and March 2006 were included. After 1 week of H. pylori eradication triple therapy (rabeprazol 10 mg, clarithromycin 500 mg, amoxicillin 1 g bid), we evaluated gastrointestinal abnormal responses (diarrhea, bloating, constipation, abdominal pain, borborygmus, flatulence, stool frequency, belching, and nausea) and severities every week for 4 weeks. RESULTS: The incidence of diarrhea was the highest in week 1, which was 41.28% (n=28) and the lowest in week 4, which was 9.52% (n=6) and decreased from week 1 to week 4 with statistical significance (p<0.0001). The most common gastrointestinal abnormal responses were associated with flatulence in week 1 (n=21, 31.34%), week 2 (n=21, 33.33%) and abdominal distention in week 3 (n=16, 25.40%), week 4 (n=15, 23.81%). Most of gastrointestinal abnormal responses were mild, and the most common symptom with higher than moderate grade was abdominal pain (n=4, 40.00%) in week 1. Alcohol consumption and coexisting medical illness were not associated with diarrhea (p=0.0852, 0.9009 respectively). CONCLUSIONS: H. pylori eradication therapy is commonly associated with antibiotics-associated gastrointestinal abnormal responses, which may result in antibiotics intolerance and H. pylori eradication failure. Even though those symptoms are not so severe, we have to consider the gastrointestinal abnormal responses associated with H. pylori eradication, especially diarrhea.
Abdominal Pain/chemically induced ; Adult ; Alcohol Drinking ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Diarrhea/*chemically induced ; Female ; Flatulence/chemically induced/etiology ; Gastrointestinal Diseases/*chemically induced ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Young Adult

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Diarrhea ; chemically induced ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; etiology ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Radiotherapy, Conformal ; adverse effects ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; radiotherapy ; Taxoids ; administration & dosage

Antineoplastic Agents ; adverse effects ; therapeutic use ; Diarrhea ; chemically induced ; Drug Delivery Systems ; methods ; Exanthema ; chemically induced ; Humans ; Leukopenia ; chemically induced ; Lung Diseases, Interstitial ; chemically induced ; Myocardial Infarction ; chemically induced ; Neoplasms ; drug therapy ; Tumor Lysis Syndrome ; etiology