Development of a quality assurance system in radiation oncology: A 12-year experience in a University Hospital.

PURPOSE: This study aimed to report 12 years of experience in the development of a quality assurance system in radiation oncology in a university hospital. MATERIAL AND METHODS: We developed the Quality Assurance Program in Radiation Oncology (QUAPRO) in 2008 to detect treatment deviation in the radiotherapy (RT) process with three steps of near-miss detection: simulation and prescription (primary check, PC), treatment planning (secondary check, SC), and treatment delivery process (tertiary check, TC). We transferred our paper-based medical records to electronic-based radiotherapy information systems (RTISs) in 2013. QUAPRO was completely integrated into RTIS in 2017. Since then, electronic-based incident reporting has been conducted. The program is called the Radiation Incident Learning System (RILS). The near-miss rates were compared during the three time periods: 2008-2012, 2013-2017, and 2017-2020. RESULTS: Five years of paper-based QUAPRO for 2008-2012 demonstrated a fluctuation in the checking ratio, with a gradually increasing rate of near misses of 3.5-19.7%. After electronic-based medical records were developed in 2013, the results revealed a dramatic increase from a rate of 2.7 to 4.2 in the number of checks per patient and achieved an increased rate of near misses of 24.7% for PC, SC, and TC. The rate of near misses gradually decreased to 5.3% after 2017 because of RT workflow improvement. CONCLUSION: The analysis of 12 years in near-miss data reflected the effectiveness of our quality assurance program. The QUAPRO system can detect near-miss incidents in the whole RT workflow and illustrate the detection improvement when integrated into electronic-based medical records. Regular feedback and exploration of near-miss reporting are recommended for proper RT workflow improvement.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

OBJECTIVES: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

Effect of Deformation Methods on the Accuracy of Deformable Image Registration From Kilovoltage CT to Tomotherapy Megavoltage CT.

INTRODUCTION: The registration accuracy of megavoltage computed tomography images is limited by low image contrast when compared to that of kilovoltage computed tomography images. Such issues may degrade the deformable image registration accuracy. This study evaluates the deformable image registration from kilovoltage to megavoltage images when using different deformation methods and assessing nasopharyngeal carcinoma patient images. METHODS: The kilovoltage and the megavoltage images from the first day and the 20th fractions of the treatment day of 12 patients with nasopharyngeal carcinoma were used to evaluate the deformable image registration application. The deformable image registration image procedures were classified into 3 groups, including kilovoltage to kilovoltage, megavoltage to megavoltage, and kilovoltage to megavoltage. Three deformable image registration methods were employed using the deformable image registration and adaptive radiotherapy software. The validation was compared by volume-based, intensity-based, and deformation field analyses. RESULTS: The use of different deformation methods greatly affected the deformable image registration accuracy from kilovoltage to megavoltage. The asymmetric transformation with the demon method was significantly better than other methods and illustrated satisfactory value for adaptive applications. The deformable image registration accuracy from kilovoltage to megavoltage showed no significant difference from the kilovoltage to kilovoltage images when using the appropriate method of registration. CONCLUSIONS: The choice of deformation method should be considered when applying the deformable image registration from kilovoltage to megavoltage images. The deformable image registration accuracy from kilovoltage to megavoltage revealed a good agreement in terms of intensity-based, volume-based, and deformation field analyses and showed clinically useful methods for nasopharyngeal carcinoma adaptive radiotherapy in tomotherapy applications.

Accuracy of eight deformable image registration (DIR) methods for tomotherapy megavoltage computed tomography (MVCT) images.

INTRODUCTION: The application of deformable image registration (DIR) to megavoltage computed tomography (MVCT) images benefits adaptive radiotherapy. This study aims to quantify the accuracy of DIR for MVCT images when using different deformation methods assessed in a cubic phantom and nasopharyngeal carcinoma (NPC) patients. METHODS: In the control studies, the DIR accuracy in air-tissue and tissue-tissue interface areas was observed using twelve shapes of acrylic and tissue-equivalent material inserted in the phantom. In the clinical studies, the 1st and 20th fraction MVCT images of seven NPC patients were used to evaluate application of DIR. The eight DIR methods used in the DIRART software varied in (i) transformation framework (asymmetric or symmetric), (ii) DIR registration algorithm (Demons or Optical Flow) and (iii) mapping direction (forward or backward). The accuracy of the methods was compared using an intensity-based criterion (correlation coefficient, CC) and volume-based criterion (Dice's similarity coefficient, DSC). RESULTS: The asymmetric transformation with Optical Flow showed the best performance for air-tissue interface areas, with a mean CC and DSC of 0.97 ± 0.03 and 0.79 ± 0.11 respectively. The symmetric transformation with Optical Flow showed good agreement for tissue-tissue interface areas with a CC of (0.99 ± 0.01) and DSC of (0.89 ± 0.03). The sequences of target domains were significantly different in tissue-tissue interface areas. CONCLUSIONS: The deformation method and interface area affected the accuracy of DIR. The validation techniques showed satisfactory volume matching of greater than 0.7 with DSC analysis. The methods can yield acceptable results for clinical applications.

Evaluation of Deformable Image Registration (DIR) Methods for Dose Accumulation in Nasopharyngeal Cancer Patients during Radiotherapy.

INTRODUCTION: Deformable image registration (DIR) is used to modify structures according to anatomical changes for observing the dosimetric effect. In this study, megavoltage computed tomography (MVCT) images were used to generate cumulative doses for nasopharyngeal cancer (NPC) patients by various DIR methods. The performance of the multiple DIR methods was analysed, and the impact of dose accumulation was assessed. PATIENTS AND METHODS: The study consisted of five NPC patients treated with a helical tomotherapy unit. The weekly MVCT images at the 1st, 6th, 11th, 16th, 21st, 26th, and 31st fractions were used to assess the dose accumulation by the four DIR methods. The cumulative dose deviations from the initial treatment plan were analysed, and correlations of these variations with the anatomic changes and DIR methods were explored. RESULTS: The target dose received a slightly different result from the initial plan at the end of the treatment. The organ dose differences increased as the treatment progressed to 6.8% (range: 2.2 to 10.9%), 15.2% (range: -1.7 to 36.3%), and 6.4% (range: -1.6 to 13.2%) for the right parotid, the left parotid, and the spinal cord, respectively. The mean uncertainty values to estimate the accumulated doses for all the DIR methods were 0.21 ± 0.11 Gy (target dose), 1.99 ± 0.76 Gy (right parotid), 1.19 ± 0.24 Gy (left parotid), and 0.41 ± 0.04 Gy (spinal cord). CONCLUSIONS: Accuracy of the DIR methods affects the estimation of dose accumulation on both the target dose and the organ dose. The DIR methods provide an adequate dose estimation technique for observation as a result of inter-fractional anatomic changes and are beneficial for adaptive treatment strategies.

Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: a single institution experience from Thailand.

BACKGROUND: To report the results of combined chemoradiation (CCRT) with cisplatin versus carboplatin in locally advanced cervical carcinoma. METHODS: From 2009 to 2013, 255 patients with stage IIB-IVA cervical carcinoma, according to FIGO staging were prospectively assigned to be treated with pelvic radiotherapy followed by brachytherapy given concurrently with cisplatin or carboplatin in the treatment of locally advanced cervical cancer. Treatment outcomes and toxicitiy were evaluated. RESULTS: Two-hundred and thirteen patients could be evaluated. At a median follow-up time of 43 months (6-69 months), the 3-year local control, disease-free survival, metastasis-free survival and overall survival rates were 93, 80.8, 85.0 and 87.3 %, respectively. No statistical difference in terms of local control, disease-free survival, metastasis-free survival and overall survival rates between cisplatin and carboplatin treatments was observed in this study. Eighty-six percents of the patients in the carboplatin group could receive more than 4 cycles, while there were only 72 % in the cisplatin group who completed more than 4 cycles (p = 0. 02). In terms of acute toxicity, cisplatin caused significantly more anemia (p = 0.026), neutropenia (p = 0. 044) and nephrotoxicity (p = 0. 031) than carboplatin. No difference in late toxicity was observed in this study. CONCLUSION: Carboplatin yielded comparable results to cisplatin in concurrent chemo-radiation for locally advanced cervical cancer. In addition, carboplatin was associated with a better compliance rate and was associated with less of anemia, neutropenia and nephrotoxicity.

University Cooperation Platform (UCP) between Christian-Albrechts-University Kiel (Germany) and Chiang Mai University (Thailand): implementation of image-guided gynecological brachytherapy.

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.

Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

PURPOSE: Lapatinib 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 METHODS: This 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. RESULTS: The 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.

The effects of two HDR brachytherapy schedules in locally advanced cervical cancer treated with concurrent chemoradiation: a study from Chiang Mai, Thailand.

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.

Capecitabine and weekly paclitaxel as first-line therapy in Thai patients with metastatic breast cancer.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.

Preliminary results of MRI-guided brachytherapy in cervical carcinoma: the Chiangmai University experience.

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.

Preliminary results of conformal computed tomography (CT)-based intracavitary brachytherapy (ICBT) for locally advanced cervical cancer: a single institution's experience.

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.

A retrospective study comparing hypofractionated radiotherapy and conventional radiotherapy in postmastectomy breast cancer.

BACKGROUND: 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. MATERIAL AND METHOD: 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. RESULTS: 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. CONCLUSION: HFRT is as effective as CRT in postmastectomy breast cancer.

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.

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.

Phase II study of capecitabine (Ro 09-1978) in patients who have failed first line treatment for locally advanced and/or metastatic cervical cancer.

PURPOSE: 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 AND METHODS: 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. RESULTS: 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. CONCLUSION: Capecitabine as a monotherapy has a modest response in locoregional failure and/or metastatic cervical cancer who have failed first line therapy.

Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Capecitabine-based chemoradiotherapy with adjuvant capecitabine for locally advanced squamous carcinoma of the uterine cervix: phase II results.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Capecitabine-based chemoradiotherapy with adjuvant capecitabine is a well-tolerated option with an early signal of efficacy meriting further evaluation.

The study of cisplatin and vinorelbine in metastatic uterine cervical cancer.

OBJECTIVE: To determine the therapeutic efficacy of cisplatin in combination with vinorelbine in the treatment of patients with metastatic cervical cancer. MATERIAL AND METHOD: 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. RESULTS: 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. CONCLUSION: Cisplatin-vinorelbine is an active and well-tolerated regimen in metastatic cervical carcinoma. These results require confirmation.

Taxotere, cisplatin, fluorouracil, and leucovorin (TPFL)as induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck.

UNLABELLED: This is a phase II clinical study conducted to evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Twenty-one previously untreated patients with stage III or IV SCCHN were treated with TPFL. Patients who received a complete response (CR) or partial response (PR) to three cycles of TPFL received definitive radiation therapy. The primary end points were toxicity and response to TPFL. RESULTS: Fifty cycles were administered to 21 patients. The major acute toxicities to TPFL were mucositis, fatigue, and anorexia. Additional major toxicities were neutropenia, anemia, and weight loss. The overall clinical response rate to TPFL was 47.6% , with 19% CRs and 28.6% PRs. In addition, the median time to progression and overall survival time were 49.2 months and 42.7 months, respectively. CONCLUSION: TPFL has an acceptable toxicity profile for patients with locally advanced squamous cell carcinoma of the head and neck and may hold curative potential for some patients with surgically unresectable or medical inoperable situations. OBJECTIVE: To evaluate the efficacy and safety to TPFL regimen for locally advanced squamous cell carcinoma of the head and neck.