[Show abstract][Hide abstract] ABSTRACT: Starting in 1999, the University Cooperation Platform (UCP) implemented an exchange program of researchers and clinicians/physicists between the Christian-Albrechts-University Kiel in Germany and Chiang Mai University in Thailand, to initiate a sustainable base for long-term development of image-guided brachytherapy and in general for high-technology radiotherapy in Chiang Mai. A series of UCP protocols, based constructively on each other, were performed and evaluated at intermediate term follow-up. The first protocol, addressing computed tomography (CT)-optimized brachytherapy for advanced cervical cancer (n = 17), showed a significant reduction of D2cc for the bladder and sigmoid (p < 0.001) while maintaining a very high dose in D90 high-risk clinical target volume (HR-CTV) in comparison with standard point-based planning. In addition, after a follow-up of 19 months no tumor relapse was observed. The second UCP protocol, testing the impact of magnetic resonance imaging (MRI) guidance (n = 15) in patients with cervical cancer, proved significantly smaller D2cc doses for the bladder, rectum, and sigmoid (p = 0.003, p = 0.015, and p = 0.012), and secured highly curative mean doses in D90 HR-CTV of 99.2 Gy. The acute and late toxicity was excellent without any observed grade 3 or higher morbidity. In the third protocol, the combination of image-guided brachytherapy (IGBT) and whole pelvis intensity-modulated external beam radiotherapy (WP-IMRT) (n = 15) reaffirmed the significant reduction of D2cc doses for the bladder, rectum, and sigmoid (p = 0.001 or p < 0.001) along with high equivalent dose at 2 Gy (EQD2) in the HR-CTV, and demonstrated very low acute therapy-related toxicity in absence of grade 3 morbidity. The implementation of transabdominal ultrasound (TAUS) was the focus of the fourth UCP project aiming a more generous potential use of image-guidance on long-term, and enhancing the quality of soft tissue assessment complementary to conventionally planned gynecological brachytherapy. Analyses in 29 patients revealed significantly reduced OARs doses in bladder with a total EQD2 > 80 Gy for bladder in only 17.2% versus 62.1% in conventional planning, and in rectum EQD2 > 75 Gy in 44.8% versus 79.3%, respectively. In conclusion, analyses revealed excellent results for the high-dose-rate IGBT in patients with advanced gynecological cancer both by using CT and MRI, and/or the combination with WP-IMRT. They also define MRI as gold standard for soft tissue assessment and to determine more accurately HR-CTV. The use of TAUS-guidance adds quality aspects to the "classical" conventional X-ray based planning, especially in terms of real-time measures and adequate soft tissue information, and may lower significantly the dose in OARs. The review of all UCP-results reconfirms the importance of the established program that will continue to operate with subsequent projects.
Journal of Contemporary Brachytherapy 02/2015; 7(1):86-92. DOI:10.5114/jcb.2015.49444
[Show abstract][Hide abstract] ABSTRACT: PURPOSELapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).Patients And methodsThis phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety.ResultsThe addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. CONCLUSION
This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.
[Show abstract][Hide abstract] ABSTRACT: The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease.
This open-label, single-center, non-comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m(2) in a 3-week cycle for a total of six cycles.
After a median follow up of 13.4 months, an overall objective response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity).
A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.
[Show abstract][Hide abstract] ABSTRACT: Efficacy of different schedules of HDR brachytherapy in concurrent chemoradiotherapy was evaluated. The study compared the effectiveness of the two HDR brachytherapy schedules which have the same Biological Effective Dose (BED) in locally advanced cervical carcinoma that was treated with concurrent chemoradiotherapy. Included in the study were 377 randomly selected patients with advanced carcinoma of the cervix uteri who were treated during the period 2004-2006. Patients were divided into Group I: 7.2 Gy × 3 fractions and Group II: 6 Gy × 4 fractions. With a median follow-up time of 35 months, local control, disease-free survival and overall survival rates were 80.8%, 63.4%, 98.8% in group I and 86.7%, 63.8%, 97.3% in group II, respectively. There was no statistical significance in terms of local control, disease-free survival, overall survival and complication rates between the two treatment schedules which could be observed. Seven patients in group I developed acute grade 2-4 GI toxicities and two patients in group II. In GU toxicities, there were three patients in group I and three patients in group II who developed grade 2-4 toxicities. In late toxicity, no patient developed grade 3-4 GU toxicities in group I while two patients developed grade 3-4 GU toxicities in group II. In GI toxicities, there were five and six patients in group I and group II, respectively, who developed grade 3-4 severity. Both HDR schedules seem to be safe and effective for the treatment of locally advanced cervical cancer.
Journal of Radiation Research 03/2012; 53(2):281-7. DOI:10.1269/jrr.11038 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was performed to evaluate the feasibility of magnetic resonance imaging (MRI) in the treatment planning of image-guided brachytherapy for cervical carcinoma. Seventeen consecutive patients with locally advanced cervical cancer were enrolled in the study. Fifteen patients could be evaluated. When comparing the tumor at diagnosis (GTV-Dx) and the tumor at the first brachytherapy (GTV-BT), 11 of 15 patients showed a tumor regression of more than 80% while only four patients had less than 80% tumor regression. The mean D90 of HR-CTV and the calculated D2cc of the bladder, rectum, and sigmoid were 99.2 ± 11 Gy, 87.7 ± 5.7 Gy, 68.4 ± 5.4 Gy and 70.3 ± 6.8 Gy, respectively. No grade 3-4 acute toxicity was observed. The MRI can be a valuable tool for evaluating tumor response after external beam radiotherapy (EBRT) and is very helpful for prognosis prediction by residual GTV evaluation. Furthermore, MRI-guided brachytherapy allowed us to optimize the dose for both the target volumes and the OARs.
Journal of Radiation Research 01/2012; 53(2):313-8. DOI:10.1269/jrr.11107 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
Two cycles of oxaliplatin 130 mg/m(2) plus FA 20 mg/m(2) bolus for 5 days and 5-FU 350 mg/m(2) 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.
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.
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.
Biomedical Imaging and Intervention Journal 10/2011; 7(4):e25. DOI:10.2349/biij.7.4.e25
[Show abstract][Hide abstract] ABSTRACT: Intracavitary brachytherapy using tandem and ovoids is an important component of definitive treatment for cervical cancer. In the present study, we analyzed the dose-volume histograms (DVHs) of the tumor volume and organs at risk including the sigmoid colon by CT-based treatment planning for high dose rate (HDR) intracavitary brachytherapy (ICBT) in cervical cancer. Seventeen patients with carcinoma of the cervix uteri were treated with external beam radiotherapy plus concurrent chemotherapy. For brachytherapy, the planning procedure started by performing a conventional plan which prescribed a dose of 6.5-7 Gy per fraction to point A, then optimized the dose based on CT imaging. Volumes and DVHs were calculated for the HR-CTV, bladder, rectum and sigmoid colon. The mean BED(2Gy) total doses of post-optimized plans of HR-CTV, bladder, rectum and sigmoid colon were: 89.6, 94.1, 74.0 and 69.8 Gy, respectively. For conventional plans, the calculated mean BED(2Gy) total doses of HR-CTV, bladder, rectum and sigmoid colon were 92.2, 120.1, 75.7 and 78.3 Gy, respectively. This study showed statistical significant higher BED(2Gy) total doses for bladder and sigmoid colon (p < 0.001) using conventional plans versus post-optimized, CT-based plans, while no difference between HR-CTV and rectum BED(2Gy) total doses could be detected. After a median follow-up of nineteen months, all seventeen patients had a clinical complete response. Two patients developed distant metastasis. Compared with conventional treatment, CT based brachytherapy planning was very effective in reducing doses to OARs, especially bladder and sigmoid colon whilst maintaining a high therapeutic dose for tumor target volumes in the treatment of cervical carcinoma.
Journal of Radiation Research 09/2011; 52(5):634-40. DOI:10.1269/jrr.10154 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The conventional radiotherapy (CRT) in postmastectomy breast cancer is 1.8-2.0 Gy daily for 25 fractions, while hypofractionated radiotherapy (HFRT) delivered dose in fewer fractions with larger radiation intensity. The present study compares the efficacy of HFRT and CRT.
From 2004 to 2006, 215 patients were retrospectively reviewed. Sixty seven patients received CRT and 148 patients received HFRT (2.65 Gy in 16-18 fractions). Five-year locoregional control (LRC), disease free survival (DFS), overall survival (OS) and toxicities were analyzed.
Median follow-up was 39 months. Five-year LRC was 86.6% in CRT and 85.8% in HFRT (p = 0.852). Five-year DFS was 62.7% and 69.6% (p = 0.136) in CRTand HFRT respectively. Patients who received HFRT had significant increase in 5-year OS (62.7% and 73.0% (p = 0.048). No difference of toxicities including changes in chest wall appearance, skin fibrosis, brachial plexopathy, arm edema, pulmonary fibrosis, rib fractures and cardiovascular events was found between two groups.
HFRT is as effective as CRT in postmastectomy breast cancer.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 03/2011; 94 Suppl 2:S94-102.
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Radiation Research 01/2011; 52(1):9-14. DOI:10.1269/jrr.10021 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to evaluate the efficacy and safety of capecitabine in cervical cancer patients who have locoregional failure and/or distant metastasis and failed first line therapy. The efficacy of capecitabine is determined by the overall response rate (ORR) according to WHO criteria for response and the safety by adverse event (AE) and tolerability profiles according to NCI CTC version 2.0.
Patients with loco-regional failure and/or metastatic cervical cancer who have failed first line therapy were enrolled into the study. The patient received capecitabine 1, 250 mg/m2 twice daily for 14 consecutive days with 7 days rest (21-day cycle). The treatment was continued for up to six cycles.
Forty-five patients previously treated by single or combination of surgery, or chemotherapy or radiotherapy were enrolled for study. Thirty-seven of 45 patients (82%) received at least 2 cycles of treatment and they were evaluated for response. The intention to treat analyses revealed 6/45(13%) ORR, 1/45 (2%) CR and 5/45 (11%) PR. Twenty-four patients (53%) had stable disease and 20% had progression of the disease. The median time to progression was 4. 1 months and the median overall survival was 9.3 months.
Capecitabine as a monotherapy has a modest response in locoregional failure and/or metastatic cervical cancer who have failed first line therapy.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2010; 37(7):1271-5.
[Show abstract][Hide abstract] ABSTRACT: Radiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients.
Patients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication.
A total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001).
Live lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.
[Show abstract][Hide abstract] ABSTRACT: Women with cervical cancer that is too big to be removed by surgery, or has spread to the tissues around the cervix (often called locally advanced cervical cancer) may be treated with radiotherapy (treatment with x-rays). They might also get chemotherapy (drug treatment) alongside radiotherapy. This is called chemoradiotherapy (or chemoradiation). This review brought together 18 randomised controlled trials (RCTs) that were carried out in many countries. The results of the review showed that women who had chemoradiotherapy for cervical cancer were likely to live for longer than women who had just radiotherapy. Five years after being treated, 66 out of every 100 women who received chemoradiotherapy were still alive compared with 60 out of every 100 who just had radiotherapy. Women who received chemoradiotherapy were also less likely to have the cancer come back or spread to other parts of the body. Chemoradiotherapy helped all women, even those with bigger tumours, or tumours that had spread more. Also, the different drugs that had been used in the trials (cisplatin, 5-fluourouracil or mitomycin-C) all helped women to live longer or stop the cancer from coming back or spreading. Some of the short term side effects were worse for women who received chemoradiotherapy. Doctors can usually help women to cope with the short term side effects of their treatment. Unfortunately, there was not enough information to be certain whether the long-term side effects are worse with chemoradiotherapy or not. The review also seemed to show that women who have extra chemotherapy (after they have had chemoradiotherapy) live longer than those who just have chemoradiotherapy. However, the researchers are less certain about these results and suggest that new RCTs are needed to find out whether giving extra chemotherapy is better for women with cervical cancer, or not.
[Show abstract][Hide abstract] ABSTRACT: Cisplatin-based chemoradiotherapy is the standard treatment for locally advanced cervical cancer but causes considerable toxicity. Capecitabine and radiotherapy show preclinical synergy and clinical activity. The activity, tolerability, and oral administration of capecitabine make it an attractive adjunctive therapy.
In this phase II study, patients with untreated International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer received capecitabine, 825 mg/m(2) twice daily (Monday-Friday), during radiation (45 Gy per 25 fractions external-beam radiotherapy and 26 Gy high-dose rate brachytherapy to point A, maximum 8 weeks), followed by six cycles of capecitabine, 1,000 mg/m(2) twice daily (days 1-14 every 21 days).
The overall response rate in 60 patients was 88% (95% confidence interval [CI], 77.4%-95.2%), including complete responses (CRs) in 80% of patients. The 1-year progression-free and overall survival rates were 86% (95% CI, 77%-95%) and 95% (95% CI, 89%-100%), respectively. At 23 months, 76% of patients were progression free (95% CI, 65%-88%) and CR was maintained in 90% (95% CI, 81%-99%) of the 48 patients achieving a CR. There were three grade 3 or 4 treatment-related events: reversible grade 4 hypokalemia, grade 3 diarrhea, and grade 3 hand-foot syndrome.
Capecitabine-based chemoradiotherapy with adjuvant capecitabine is a well-tolerated option with an early signal of efficacy meriting further evaluation.
The Oncologist 09/2009; 14(8):828-34. DOI:10.1634/theoncologist.2009-0041 · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the therapeutic efficacy of cisplatin in combination with vinorelbine in the treatment of patients with metastatic cervical cancer.
a total of 17 patients were enrolled in the present study. The median age was 46 years (38-65). There were 6 patients who were diagnosed as stage IVB cervical cancer without previous treatment. The patients were planned to receive cisplatin 80 mg/m2 on day 1 and vinorelbine at 30 mg/m2 on day 1 and 8 every 3 weeks.
Fifteen patients were available for evaluation: 2 (13.3%) achieved a complete response, 8 (53.4%) partial responses, 3 (20%) stable diseases and 2 (13.3%) progression of the disease. Myelosuppression was the major toxicity Grade 3-4 toxicities include 66.7% hemoglobin and 26.7% neutropenia. No other significant side effects were found.
Cisplatin-vinorelbine is an active and well-tolerated regimen in metastatic cervical carcinoma. These results require confirmation.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 07/2009; 92(6):836-40.