Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial.

BACKGROUND AND PURPOSE: To evaluate the efficacy and the safety of WF10 as adjunct to standard treatment in the management of late hemorrhagic radiation cystitis compared to standard treatment alone. PATIENTS AND METHODS: Cervical cancer patients with Grade 2 or 3 late hemorrhagic radiation cystitis, were randomized and treated with WF10 0.5 ml/kg body weight, diluted in physiological saline or 5% dextrose water 250 ml, intravenous infusions over 2 h on 5 consecutive days, every 3 weeks for 2 cycles plus standard treatment (WF10 group) or standard treatment alone (control group). Fifty patients in each group were evaluated by questioning; urinalysis and cystoscopy during a 1 year follow up. RESULTS: At week 7, 37 patients (74%) in the WF10 group and 32 patients (64%) in the control group showed complete resolution in objective hematuria (P = 0.28). Significantly lower use of antibiotics (P = 0.002) and antispasmodics (P < 0.001) was found in the WF10 group. Among the responders, 24 patients (77%) in the control group experienced recurrent objective hematuria, whereas in the WF10 group only 17 patients (47%) experienced a recurrence (P = 0.01). Recurrence of objective hematuria occurred significantly faster in the control group as evidenced by Kaplan-Meier and log-rank statistics (P = 0.004), suggesting a long-term effect of WF10. Cystoscopy, at the end of the treatment period and after the one year follow up showed overall improvement without significant difference between two groups. No severe toxicity was monitored. CONCLUSIONS: WF10 therapy is a safe, non-invasive and convenient method in the management of late hemorrhagic radiation cystitis. WF10 therapy, as adjunct to standard treatment, has significantly reduced recurrence of objective hematuria, compared to standard treatment alone, during a one year follow up.     

Two-year outcome of concurrent chemoradiation with carboplatin with or without adjuvant carboplatin/fluorouracil in nasopharyngeal cancer: A multicenter randomized trial

BackgroundAccording to the noninferiority result of chemoradiation with carboplatin in our previous nasopharyngeal carcinoma (NPC) study along with the inconclusive data on the efficacy of adjuvant chemotherapy (AC) following concurrent chemoradiotherapy (CCRT), we designed to assess the role of adjuvant carboplatin/fluorouracil following CCRT with carboplatin in locoregionally advanced NPC.Materials and MethodsA multicenter randomized trial was conducted at 5 cancer centers in Thailand. We enrolled in stage T2N0M0-T4N2M0 (American Joint Cancer Committee 7th edition) WHO Type 2 NPC patients. N3 or metastatic disease patients were excluded. Participants were randomized into 2 groups: CCRT plus AC group vs the CCRT alone group. Patients in both groups received weekly carboplatin 100 mg/m² for 6 cycles concurrently with radiotherapy 69.96-70 Gy. Patients in the AC group subsequently received 3 cycles of carboplatin area under curve-5 plus 1000 mg/m²/day of fluorouracil infusion within 96 hours every 3 weeks. We report the 2-year overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Treatment-related toxicities and compliance were also explored.ResultsOf 175 patients, 82 (46.9%) were assigned to the AC group, and 93 (53.1%) to the CCRT group. The compliance rate during CCRT was 90% and 86% in the AC and CCRT group, whereas 81.7% during adjuvant treatment in the AC group. With a median follow-up time of 24.4 months (interquartile range 17.9-24.4), the 2-year OS rate was 89.6% in the AC group and 81.8% in the CCRT group (P= 0.167). The 2-year DFS rate was 86.8% in the AC group and 74.6% in the CCRT group (P = 0.042). The 2-year LRFS rate was 91.5% in the AC group and 88.2% in the CCRT group (P = 0.443). The 2-year DMFS rate was 85.4% in the AC group and 79.6% in the CCRT group (P = 0.294). The most frequent serious (grade 3/4) nonhematologic toxicity was acute mucositis, which occurred 5% in the AC group vs 4% in the CCRT group (P = 0.498). For hematologic toxicity, grade 3-4 leukopenia were found 10% and 5% in the adjuvant and CCRT groups, respectively (P = 0.003). Multivariate analyses determined stage N2 disease was an adverse prognostic factor associated with shorter OS, DFS, and DMFS. And the adjuvant treatment was a significant protective factor for only DFS.ConclusionsThe addition of adjuvant carboplatin/fluorouracil following CCRT with carboplatin significantly improved 2-year DFS in stage T2N0M0-T4N2M0 NPC albeit there was a nonsignificant trend in favor of a higher 2-year OS, LRFS, and DMFS. Long-term efficacy and late toxicities of AC still require exploration.     

Impact of incomplete plan to treatment results of concurrent weekly cisplatin and radiotherapy in locally advanced cervical cancer

To evaluate the efficacy of incomplete treatment protocols of cisplatin in concurrent chemoradiation for locally advanced cervical carcinoma. This retrospective study was performed in 165 consecutively treated patients with locally advanced cervical cancer who received a weekly cisplatin regimen. The number of weekly cisplatin cycles of each patient was recorded and used to discriminate between patients. Local control, disease free survival, distant metastasis-free survival, and toxicities were calculated using the software package SPSS version 15.0. Ninety-two patients (55%) completed the planned protocol of six cycles of weekly cisplatin. With the median follow-up time of 38.2 months, the 3-year local control rate differed significantly in the two patient groups (95.4% of 6 cycles versus 84.8% of < 6 cycles; p = 0.028). No statistical significance was observed for disease-free survival (74.6% versus 74.5%; p = 0.22) and distant metastasis-free survival (76.5% vs. 75.7%; p = 0.88). In conclusion, the plan completion of concurrent cisplatin with radiotherapy was responsible for better local control. However, differences in disease-free survival and distant metastasis-free survival were not statistical significant.     

An Open-Labeled Study of Rebamipide Treatment in Chronic Gastritis Patients with Dyspeptic Symptoms Refractory to Proton Pump Inhibitors

To assess the efficacy of rebamipide therapy in chronic gastritis patients with refractory dyspeptic symptoms, we enrolled 30 patients with chronic gastritis nonresponsive to the antisecretory medications, proton pump inhibitors. Upper gastrointestinal endoscopy was performed in all patients to confirm and evaluate the severity of gastritis by gastric mucosal injury score and the histology by the updated Sydney system before and after treatment with rebamipide 300 mg daily for 8 weeks. At the end of the study, significant improvement in the scores for symptoms (epigastralgia, stomach heaviness, and abdominal fullness) and endoscopic mucosal injury were observed for all patients. The degrees of neutrophil activity in antrum and mononuclear cell inflammation in both body and antrum significantly decreased from baseline. Improvement of gastritis might be the mechanism by which rebamipide prevents gastric mucosal inflammation. In conclusion, rebamipide treatment improved symptom, endoscopic, and histologic features of chronic gastritis in patients with refractory dyspeptic symptoms.     

A phase II study of oxaliplatin with 5-FU/folinic acid and concomitant radiotherapy as a preoperative treatment in patients with locally advanced rectal cancer

Objective:

To evaluate the activity and safety of adding oxaliplatin to a standard chemoradiotherapy schema, including 5-fluorouracil (5-FU)/folinic acid (FA), in locally-advanced rectal cancer (LARC).

Methods:

Two cycles of oxaliplatin 130 mg/m² plus FA 20 mg/m² bolus for 5 days and 5-FU 350 mg/m² continuous infusion for 5 days were given during week 1 and 4 of pelvic radiotherapy 46 Gy. Patients with a T3/4 and/or node-positive rectal tumour were eligible. Surgery was performed 4–6 weeks after radiotherapy. The primary endpoint was to determine the rate of pathological response. Secondary endpoints were to assess the rate of clinical response and the safety profile.

Results:

Between March 2005 and January 2009, a total of 35 patients were enrolled. The pathological down-staging rate was 79% with a pathological complete response rate of 17%. The overall clinical response rate (assessed by computed tomography or transrectal ultrasound) was 77%. Grade 3 diarrhoea and Grade 3 neutropaenia were reported in 14% and 11% of the patients, respectively. Eleven patients did not undergo surgery: four of them refused the operation, and seven patients were inoperable due to disease progression. In 24 patients who had surgery, a sphincter-preserving procedure could be performed in 29%. At the median follow-up time of 28.1 months, 25 patients (71%) survived with no evidence of disease.

Conclusion:

The promising results in terms of pathological response, and the associated good safety profile of a regimen of oxaliplatin plus 5-FU/FA with concomitant radiotherapy, suggest that the regimen could be used in LARC.     

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer

Objective

In this study we evaluate the clinical response and safety profile of a regimen of docetaxel + carboplatin concurrent with radiotherapy (RT) in locally advanced squamous cell carcinoma of head and neck (HNSCC).

Methods

Between January 2006 and December 2008, we enrolled 38 patients (stage IVA: 29 patients; stage III: 9 patients). Fourteen had oral cavity cancer (tongue 10, buccal mucosa 2, alveolar ridge 1, floor of mouth 1), 10 had oropharyngeal cancer (base of tongue 5, tonsil 5), 13 had laryngeal cancer, and 1 had maxillary sinus cancer. Patients received concurrent docetaxel 15 mg/m² 1-h infusion plus carboplatin AUC of 2, 30-min infusion on days 1, 8, 15, 22, 29, and 36. RT began on day 1 of concurrent chemotherapy with 2 cGy/fraction, 5 fractions/week (total dose: 66-70 cGy). Tumor was assessed by CT scan 3 months post-completion of concurrent chemoradiotherapy.

Results

Thirty-five patients were evaluated (2 refused to receive all treatments, 1 had serious adverse event [rash, wheezing] from docetaxel first dose). The primary study endpoint of clinical response was achieved in 26 (74.3%) patients, 6 (17.1%) had stable disease, and 3 (8.6%) had disease progression. The 2-year disease-free survival was 62.9% (CI: 45.85-79.95%). The 2-year overall survival was 64.1% (CI: 43.52-84.68%). The most common Grade 3 toxicities were mucositis, xerostomia and dysphagia (13.9% each) and dermatitis (11%). No Grade 4 toxicities were observed.

Conclusion

In conclusion, this study with a limited number of patients, docetaxel + carboplatin concurrent with RT appears to show acceptable activity and is generally well tolerated in patients with locally advanced HNSCC.     

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.     

Risk Factors for the Development of Hepatocellular Carcinoma in Thailand

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The incidence of HCC is on the rise in Thailand, where it has become the most common malignancy in males and the third most common in females. Here, we review some of the risk factors that have contributed to this increase in HCC incidence in the Thai population. Hepatitis B virus (HBV) is the main etiologic risk factor for HCC, followed by hepatitis C virus (HCV). Patients with HBV genotype C have a higher positive rate of hepatitis B early antigen (HBeAg) and progress to cirrhosis and HCC earlier than genotype B. For HCV patients, 16% developed HCC associated cirrhosis by year 5 after diagnosis, and the cumulative risk for death from HCC at year 10 was 60%. Dietary exposure to the fungal hepatocarcinogen aflatoxin B1 has been shown to interact synergistically with HBV infection to increase the risk of early onset HCC. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. In recent years, obesity and metabolic syndrome have markedly increased the incidence of HCC and are important causes of HCC in some resource-rich regions.     

A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose–volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm³ (30.5%) and 5.4 cm³ (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6–5.9 Gy, P < 0.001 and 2.1–9.9 Gy, P < 0.001, respectively). The D_mean of the contralateral parotid decreased in 70% of the patients (range, 0.2–4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC.     

Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial

PurposeThis single centre, open labelled, randomised non-inferiority trial compared concurrent chemoradiotherapy with carboplatin versus standard concurrent chemoradiotherapy with cisplatin in patients with locoregionally advanced nasopharyngeal cancer (NPC).Patients and methodsFrom August 1999 to December 2004, 206 patients with locally advanced NPC were randomised with 101 to cisplatin arm and 105 to carboplatin arm. Planned radiotherapy was the same in both groups. All the patients were evaluated for toxicity and survival according to the as-treated principle.ResultsWith a median follow-up of 26.3 months (range 3–74.6 months), 59% of patients in the cisplatin arm completed the planned concurrent chemoradiation treatment, compared to 73% in the carboplatin arm. Forty-two percent of cisplatin patients completed the 3 cycles of adjuvant therapy compared to 70% in the carboplatin group. There were more renal toxicity, leucopenia, and anaemia in the cisplatin group, and more thrombocytopenia in the carboplatin arm. The 3 year disease free survival rates were 63.4% for the cisplatin group and 60.9% for the carboplatin group (p = 0.9613) (HR 0.70, 95% confidence interval (CI): 0.50–0.98). The 3 year overall survival rates were 77.7% and 79.2% for cisplatin and carboplatin groups, respectively (p = 0.9884) (HR 0.83, 95% CI: 0.63–1.010).ConclusionWe concluded that the tolerability of carboplatin based regimen is better than that of the cisplatin regimen. Moreover, the treatment efficacy of carboplatin arm is not different from the standard regimen in the treatment of locoregional advanced stage NPC.