Daily Cisplatin Research Articles

A comparative study of the treatment outcome of moderately accelerated radiation fractionation (with concurrent chemotherapy in daily dosing) to conventional chemo-radiotherapy in locally advanced head and neck cancers: Supportive in a resource constrained environment.

In our country, head and neck cancers account for about a third of all cancers. Moreover, the patients typically present in advanced stages, which entails intensive multimodality therapy; but there is not much scope for improved survival outcomes. In view of this, a study was conducted to know the effects of treatment intensification, wherein moderately accelerated fractionation radiotherapy was given to patients presenting with advanced cancer of head and neck. This treatment was further intensified by accompanying radiation with concurrent cisplatin chemotherapy in daily doses. The control arm received the current standard therapy of conventional fractionation radiotherapy with weekly cisplatin chemotherapy. The primary objective of the study was to determine the prospect of tumor control (TC), disease-free survival (DFS), and overall survival (OS). The secondary objective was to study acute toxicity and late toxicity of the highest grade in both treatment groups. The study was conducted on a total of 60 patients who presented with locally advanced squamous cell carcinoma of the head and neck. The 30 patients in the control group received conventional fractionated radiotherapy (five fractions per week) with weekly cisplatin chemotherapy (40 mg/m 2 ), whereas the remaining 30 in the study group received moderately accelerated radiotherapy (six fractions per week with same treatment field) along with daily cisplatin chemotherapy (6 mg/m 2 ) with a reduction in treatment time by 1 week. The overall response to therapy assessed as TC, DFS, and OS was compared, and no statistically significant difference between the two treatment arms was observed. However, the mean overall treatment time was reduced in the study group to 45 days as compared with 49 days in the control group ( P = 0.001). The acute toxicities of xerostomia ( P = 0.057) and skin ( P = 0.052) and late toxicity of aspiration/laryngeal toxicity ( P = 0.002) were higher in grade and number in the study group with accelerated fractionation. Hence, the study results suggest that it is a feasible option to combine the therapeutic benefits of accelerated fractionation radiotherapy with concurrent chemotherapy in patients with locally advanced head and neck carcinomas. There is a significant decrease in the overall treatment time and a considerable reduction in the load on the resource-constrained healthcare system. It would be equitable to point out that higher grade of few toxicities in the acceleration arm are likely due to doses to organs at risk being intensified with accelerated fractionation, which can now be delivered in a controlled manner with the latest high precision techniques, resulting in improved toxicity profile and quality of life which is the way forward for future studies.

Abstract 6700: Characterizing circulating tumor DNA release kinetics and fragment length in a chemotherapy resistant model of esophageal adenocarcinoma

Abstract Background: While the incidence of esophageal adenocarcinoma (EAC) is rapidly increasing, the 5-year survival rate of this disease remains poor at less than 25%, with a substantial number of patients exhibiting inherent or acquired resistance to chemotherapy. Circulating tumor DNA (ctDNA) isolated from liquid biopsies of EAC patients holds clinical biomarker potential in this disease, but our understanding of how chemotherapy affects ctDNA release remains limited. Methods: In order to study the impact of cancer treatment on ctDNA emission in vitro, we first sought to establish a chemo-resistant model of EAC. As such, the EAC cell line OE19 was exposed to discontinuous cisplatin treatments for three months in order to establish drug resistance. Following this, established chemo-resistant OE19 cells and parental (chemo-sensitive) OE19 cells were exposed to five daily cisplatin treatments, and cell culture supernatant was collected every day throughout treatment. ctDNA was subsequently isolated from cell culture supernatant and quantified by Qubit fluorometer dsDNA HS assay. ctDNA quantities were additionally assessed by droplet digital PCR (ddPCR) assay using primers and probes targeting the TP53 N310K mutation in the OE19 cell line. Finally, ctDNA fragment lengths were analyzed using the Agilent Bioanalyzer 2100. Results: A chemo-resistant model of the OE19 cell line was established, as exemplified by marked morphological changes in the cells and significantly increased cell viability determined by CCK8 assay after 48-hour treatments of various doses of cisplatin (p<0.05). ctDNA levels, as measured by both Qubit fluorometer and mutant copies detected by ddPCR assay, increased after chemotherapy treatment for both chemo-sensitive and resistant cells. Notably, ctDNA emission was higher with larger amounts cell death, with chemo-sensitive cells emitting significantly higher levels of ctDNA compared to chemo-resistant cells throughout treatment (p<0.05). Fragmentomics analysis revealed ctDNA peaks corresponding to apoptosis (~167 bp) and necrosis (~10,000 bp). Moreover, chemotherapy treatment caused a shift in average fragment size, with larger fragments being observed during chemotherapy treatment in both chemo-sensitive and resistant cells. Conclusion: This study reveals that in vitro cancer models can be used to successfully study ctDNA emission during pre-clinical drug analyses. ctDNA release was found to be correlated to cytotoxicity and cell death, providing us with valuable insight into how clinical liquid biopsy data should be interpreted. Finally, fragment size analysis of ctDNA reveals a potential novel biomarker for treatment response in cancer patients. Citation Format: Alexandra Bartolomucci, Sarah Tadhg Ferrier, Thupten Tsering, Xin Su, Jonathan Cools-Lartigue, Julia V. Burnier. Characterizing circulating tumor DNA release kinetics and fragment length in a chemotherapy resistant model of esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6700.

Prediction model of acute kidney injury induced by cisplatin in older adults using a machine learning algorithm.

BackgroundEarly detection and prediction of cisplatin-induced acute kidney injury (Cis-AKI) are essential for the management of patients on chemotherapy with cisplatin. This study aimed to evaluate the performance of a prediction model for Cis-AKI.MethodsJapanese patients, who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital, were enrolled in the study. The main metrics for evaluating the machine learning model were the area under the curve (AUC), accuracy, precision, recall, and F-measure. In addition, the rank of contribution as a predictive factor of Cis-AKI was determined by machine learning.ResultsA total of 1,014 and 226 patients were assigned to the development and validation data groups, respectively. The current prediction model showed the highest performance in patients 65 years old and above (AUC: 0.78, accuracy: 0.77, precision: 0.38, recall: 0.70, F-measure: 0.49). The maximum daily cisplatin dose and serum albumin levels contributed the most to the prediction of Cis-AKI.ConclusionOur prediction model for Cis-AKI performed effectively in older patients.

Comparison of Response to the Concurrent Low Dose Daily Cisplatin Vs Weekly Cisplatin Vs Three Weekly Cisplatin with External Beam Radiotherapy in Carcinoma Cervix Patients of Stage IIB, IIIA & IIIB: A Prospective Study from Single Institution

Introduction: Cervical cancer continues to be a major public health problem affecting middle-aged women, particularly in less-resourced countries. External beam radiation therapy along with intra cavitary insertion has long been the treatment of choice for locally advanced (IIB-IVA) cervical cancer, but long-term successes are limited in terms of pelvic recurrence or distant metastasis. Outcome of low dose daily versus weekly versus three weekly Cisplatin concurrent with External beam radiotherapy in locally advanced cervical carcinoma was compared in this study.
 Methods: A prospective cross sectional study was carried out in J K cancer institute, Kanpur. Total 60 patients of cervical cancer were randomized into 3 arms. Arm I, Arm II and Arm III received External beam radiotherapy concurrent with either daily (8mg/m2), weekly (40 mg/m2) or three weekly (100 mg/m2) Cisplatin respectively. External beam radiotherapy was given with a dose of 50 Gy / 25 # / 5 week / 2 field or 4 field. Patients were evaluated weekly during treatment and afterwards up to 1year. Results: Most of the patients were from fourth and fifth decade, low socioeconomic strata and illiterate. Majority of the cases belong to squamous cell carcinoma (96.6%) and stage III B (55%). Objective response in arm I was 80.0%, in arm II was 75.0% and in arm III was 60.0% respectively. Statistically significant difference was noted between arm III and Arm I (80%Vs60% p<0.05). Results were better in arm I as compare to arm II but not statistically significant. (80%Vs75% P>0.05)
 Conclusions: This study showed that response was better in ARM I as compared to ARM III and best results was seen with Cisplatin concurrent daily with radiation.
 Keywords: Cisplatin, concurrent chemotherapy, daily, weekly, three weekly, carcinoma cervix

Comparison of daily low dose cisplatin versus weekly cisplatin concurrently with radiotherapy during head and neck cancer

Head and neck cancers can arise in the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid, and salivary glands and include a variety of histopathologic tumours. Squamous cell cancer (SCC) is the most common pathological type of head and neck cancer.This is prospective, Observational and comparative study.The diagnosis of untreated squamous cell carcinoma of the head and neck region, i.e., oral cavity, oropharynx, hypopharynx, or larynx in advanced stage III, IVA or IVB SCCHN was confirmed by a radiation oncologist prior to the initiation of the treatment. Patients were considered to comply with radiation treatment if they completed 70 Gy within 45 days. Chemotherapy compliance (six cycles in weekly or 28–30 cycles in daily cisplatin) were 63% and 73%, respectively. The primary reason for noncompliance toward chemotherapy (37% vs. 27% in weekly vs. daily Cisplatin studies, respectively) was due to the development of excessive toxicity. This also included those who left treatment midway (due to any reason) or died during therapy.Therefore, if an intensified treatment protocol has to be used, i.e. modest acceleration along with either “weekly” or “daily” cisplatin, both can be used, provided patients are selected properly and due attention is paid to timely and adequate supportive care.

A novel approach to neoadjuvant chemoradiation for soft tissue sarcoma using cisplatin and adriamycin.

e22515 Background: Soft tissue sarcomas (STS) are heterogeneous solid tumors of mesenchymal cell origin, often difficult to manage. Local recurrence of extremity STS with surgery alone ranges from 5-20% with amputation ; 40% with wide excision. Neoadjuvant therapies are used to improve surgical outcomes. There is currently no recognized optimal neoadjuvant chemoradiation regimen prior to resection of STS. At our institution, we have piloted a neoadjuvant regimen of daily Cisplatin with infusional Adriamycin concurrent with radiation to assess its impact on surgical outcomes and tumor control. Methods: Patients diagnosed with STS of any site were treated neoadjuvantly with Cisplatin 6mg/m2 IV over 3-5 mins given 20 to 30 minutes before radiation (5 days) for 6 weeks. Adriamycin was given in the inpatient setting at 12.5 mg/m2 IV over 24 hours on days 1-4, weeks 1 and 4. The radiation dose was 54 Gy in 30 fractions. More than 50% of patients were treated with IMRT planning. Results: Since 2011, 12 STS patients were treated preoperatively with this regimen. Of these patients, 9 underwent surgery. Six of the 9 surgical patients received this neoadjuvant protocol followed by resection in the upfront setting. All of the 6 upfront patients had negative surgical margins; all of these patients had grade 3 tumors. Necrosis was reported based on the FNCLCC grading system. The average percent of necrosis was 96.3% (95% confidence interval 50.4%, 99.8%). Toxicity: Reported according to the RTOG/EORTC Radiation toxicity grading system. Of all patients, grade 1-2 skin toxicity predominated (75%). No grade 4 toxicity reported. Hematologic toxicity: Of all patients, grade 2-3 hematologic toxicity during neoadjuvant chemotherapy was reported in 83% of patients; grade 4 in 1 patient. No febrile neutropenia occurred. Post-operative complications: Seroma/hematoma formation was the most common post-operative complication in the surgical patients. No severely delayed healing was noted. Survival:Nine of 12 patients were dead (6 of 9 surgical patients) at the time of this analysis, all of metastatic disease. Mean time to DM 7.4 months. Mean OS 10 months. Conclusions: Our novel regimen achieved high necrosis rates, and all surgical patients achieved negative margin status. These factors are prognostic and correlate with local control. The predominant pattern of failure was distant. With its acceptable toxicity, this regimen of neoadjuvant Cisplatin, Adriamycin and radiation should be examined in a randomized fashion versus neoadjuvant radiation alone to determine the long term outcomes.

Pre-hydration in cisplatin-based CCRT: Effects on tumour concentrations and treatment outcome

AimsPre-hydration is routinely applied to reduce nephrotoxicity in concurrent cisplatin-based chemo-radiotherapy (CCRT). However, pre-hydration may also have systemic effects, potentially leading to lower tumour cisplatin concentrations. We investigated the impact of pre-hydration on tumour cisplatin concentrations in mice, and on treatment outcomes in a clinical cohort study. Materials and methodsFour groups of 20 mice received either no pre-hydration prior to full-dose (6 mg/kg) or half-dose cisplatin, overnight dehydration prior to full-dose cisplatin (dehydration), or NaCl intraperitoneally prior to full-dose cisplatin (pre-hydration). Kidney function and tumour platinum concentration were measured. In patients, a retrospective study compared 2 historical NSCLC cohorts which received CCRT with daily cisplatin, with and without standard pre-hydration. Overall survival (OS) and progression free survival (PFS) were compared using Kaplan–Meier and cox-regression. ResultsPre-hydration significantly decreased cisplatin tumour concentrations in mice, comparable to mice receiving half the dose. In 419 patients (211 without and 208 with pre-hydration) with median follow-up 22 months, there were no significant differences in PFS (18 vs. 15 months) or OS (23 vs. 23 months). ConclusionPre-hydration reduces cisplatin tumour concentrations in mice, but it does not compromise treatment outcomes in NSCLC patients treated with daily cisplatin and radiotherapy.

Concurrent Daily Cisplatin and High-Dose Radiation Therapy in Patients With Stage III Non-Small Cell Lung Cancer

The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy (CCRT). Consecutive patients with stage IIIA and IIIB NSCLC (N=154) staged with 18F-fluorodeoxyglucose positron emission tomography/computed tomography were retrospectively selected (2005-2015). CCRT consisted of daily low-dose cisplatin (6mg/m2) combined with 24 fractions of 2.75Gy to a total dose of 66Gy. During a median follow-up period of 22months (range, 1-92months) the median overall survival was 36months. The 1-, 2-, 3-, and 5-year survival rates were 79% (95% confidence interval [CI], 73%-86%), 61% (95% CI, 54%-70%), 52% (95% CI, 43%-60%), and 40% (95% CI, 31%-51%), respectively. The local relapse-free survival at 5years was 55% (95% CI, 44%-69%). Metastasis-free survival at 5years was 53% (95% CI, 44%-65%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11%, among which grade 3 radiation esophagitis was 8.4%. The incidence of severe respiratory, thoracic, and mediastinal disorders (grade 3-5) was 8.4%, among which grade 3 radiation pneumonitis was 1.3%. Predictors of overall survival were lymph node gross tumor volume (GTV) (hazard ratio [HR], 1.007; 95% CI, 1.000-1.012) and sex (HR, 0.500; 95% CI, 0.320-0.870) in favor of women. Although lymph node GTV was a predictor of treatment toxicity (HR, 1.010; 95% CI, 1.000-1.013), tumor GTV was the predictor for distant metastasis during follow-up (HR, 1.002; 95% CI, 1.001-1.003). CCRT with daily low-dose cisplatin for locally advanced stage III NSCLC resulted in promising overall survival (3-year survival rate of 52% and 5-year survival rate of 40%) with low toxicity. Lymph node GTV, tumor GTV, andsex were predictors of overall survival, treatment toxicity, and distant metastasis.

Combination of Daily Low Dose Cisplatin with Thoracic Radiation in Locally Non-Small Cell Lung Cancer for Fragile Patients: An Experimental Monocentric Serie

Lung cancer incidence in the elderly is rising over year. The standard treatment for locally non-small cell lung cancer (NSCLC) is based on a combination of chemotherapy and thoracic radiation. No standard is described or validated for patients older than 70 years. The objective of this retrospective study was to evaluate the toxicities and the feasibility of daily cisplatin at a dose of 6 mg/m² during thoracic irradiation (66-70 Gray) in NSCLC with poor WHO performance status, and/or comorbidities. The second objective was to obtain a first estimation of survival for patients with stage III-IV. Between 2011 and 2015, 13 patients were retrieved from the hospital database. The median age was 71.3 years, and the most frequent histologic type was squamous cell carcinoma (69%). The most frequent grade 2 adverse events were cardiac (n=3) or digestive (n=1). No pulmonary toxicity was observed. For the 10 patients with stage III-IV, the median progression free survival was 171 months. The 1-year overall survival (OS) was 90%, and the 2-years OS was 67%. The combination of daily cisplatin with thoracic radiation is effective, and well tolerated in fragile NSCLC patients. This association should be evaluated in clinical trials.

Concurrent chemoradiotherapy with conventional fractionated radiotherapy and low-dose daily cisplatin plus weekly docetaxel for T2N0 glottic cancer

BackgroundTo assess the efficacy of concurrent chemoradiotherapy (CCRT) with daily low-dose cisplatin (CDDP) plus weekly docetaxel (DTX) for patients with T2N0 glottic cancer.MethodsBetween January 2004 and December 2013, 62 treatment-naive patients with histologically proven T2N0 glottic cancer were treated with concurrent chemoradiotherapy. Radiation therapy (RT; 2 Gy daily fractions up to a total dose of 66 Gy) was administered in combination with daily low-dose CDDP (6 mg/m2, five times a week), plus weekly DTX (10 mg/m2) for up to 4 weeks from the commencement of RT.ResultsMedian duration of follow-up was 70 months. The actuarial 3-year and 5-year overall survival rates were 95% and 93%. The 3-year and 5-year cause-specific survival rates were both 100%. The actuarial 3-year and 5-year local control rates were 94% and 94%, respectively. Hematologic toxicity (neutoropenia of severity ≥ Grade 3) was observed in 8% of the patients, and non-hematologic toxicity (radiation mucositis of severity ≥ Grade 3) developed in one patient (2%). Radiation dermatitis of severity ≥ Grade 3 and laryngeal necrosis developed in one patient.ConclusionCCRT with weekly DTX and low-dose CDDP appears to be a practical and safe modality and is expected to improve local control.Trial registrationUMIN000025046. Registered 1 October 2015, retrospectively registered.

Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer.

Aim and Objective:Weekly administration of cisplatin (cis-diamminedichloroplatinum [CDDP]) appears more feasible and substantially more popular than the 3 weekly schedules due to better compliance. Different concurrent cisplatin schedules have been attempted including a daily schedule. We did a comparison of two consecutive single arm studies, i.e., use of weekly cisplatin versus daily cisplatin when used with concurrently with a moderately accelerated radiotherapy (RT) schedule.Patients and Methods:Two prospective feasibility, safety and efficacy studies were carried out consecutively within the department. The weekly CDDP study was done from August 2003 to August 2005 and daily CDDP study was conducted from November 2005 to June 2007. Both studies included locally advanced stage III and IV squamous cell carcinoma of the head and neck region with RT dose of 70 Gy. Concurrent single-agent cisplatin was administered weekly (35 mg/m2) in the first and daily (6 mg/m2) in the second study.Results:Weekly cisplatin study had 68 and daily CDDP study had 52 patients. The median follow-up in the two studies was 93 and 63 months, respectively. Compliance in the two studies was comparable. Acute Grade III/IV mucositis and dysphagia were significantly higher in weekly cisplatin study. Late Grade II/III toxicities such as xerostomia, dysphagia, ototoxicity and nephrotoxicity were similar. The 5 years locoregional control was 18% and 25% and 5 years overall survival rate was 32% and 31% in weekly and daily cisplatin studies, respectively.Conclusions:Modest acceleration along with either weekly or daily cisplatin, whichever is possible in one's setup, is do-able, provided due attention is paid to patient selection and supportive care.

Induction docetaxel and S‐1 followed by concomitant radiotherapy with low‐dose daily cisplatin in locally advanced head and neck carcinoma

The purpose of this study was to assess the efficacy and safety of induction chemotherapy with docetaxel-S-1, and radiotherapy (RT) with concurrent daily cisplatin in locally advanced head and neck carcinoma. Fifty patients received 2 cycles of induction chemotherapy with induction chemotherapy with docetaxel and S-1, followed by 7 cycles of RT with concurrent daily cisplatin. The most frequent grade 3 to 4 hematologic toxicity was neutropenia (14%). Forty of 50 patients who completed induction chemotherapy with docetaxel and S-1 subsequently started RT with concurrent daily cisplatin, all within 3 to 4 weeks after the start of the second cycle of induction chemotherapy with docetaxel and S-1. The best response to induction chemotherapy with docetaxel and S-1 and after completion of RT with concurrent daily cisplatin was partial response (PR) in 52.5% and complete response in 47.5%, respectively. With a median follow-up of 61 months, 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 65.7%, respectively. Administration of induction chemotherapy with docetaxel and S-1 before RT with concurrent daily cisplatin chemoradiotherapy (CRT) resulted in a high response rate with good tolerability, and did not compromise subsequent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1653-E1659, 2016.

Definitive Concurrent Chemotherapy and High Dose (60-70Gy) Radiation Therapy for Esophageal Cancer

Based on the results of the intergroup-0123/RTOG 94-05 trial that demonstrated no benefit of dose escalation over 50.4 Gy in definitive chemoradiation therapy (CRT) for esophageal carcinoma, 50.4 Gy appears to be accepted as a standard dose. Radiobiologically, however, higher radiation doses, if safely delivered, could lead to better local control. We have used combination of standard FP (5-fluorouracil [5-FU] and cisplatin) chemotherapy and radiation with doses >60 Gy in the treatment of non-metastatic esophageal cancer. We report clinical outcome of the treatment protocol. Between 2002 and 2014, 78 patients with stage I-III or IV (M1 LYM) esophageal cancer were treated with CRT. Median age of the patients was 68 years (range: 46 to 84); 66 were men and 12 were women. Histology was squamous cell carcinoma in 96%. Patients were divided into 4 groups according to the stage and operability; Group 1: stage I patients (n = 10); Group 2: stage II-III operable patients (n = 16); Group 3: stage II-III (non-T4) inoperable patients (n = 19); and Group 4: stage III-IV (T4/M1 LYM) patients (n = 33). Chemotherapy protocols were either cisplatin (70 mg/m2) plus 5-FU (700 mg/m2 x 4 days) administered every 4 weeks or low-dose daily cisplatin (10 mg/m2) and 5-FU (175 mg/m2). Radiation was given by 10-MV X rays with a daily fraction of 1.8-2 Gy. Treatment volume included primary tumor plus regional lymph nodes. A total dose between 60 and 70 Gy was chosen depending on the treatment volume. Median radiation dose was 64 Gy (range: 14-70 Gy; 4 patients could not complete planned treatment). Failure was confirmed by pathology or findings of progressive disease on serial endoscopy and/or imaging studies. Overall survival (OS) and local control (LC) rates were calculated by the Kaplan-Meier method. Toxicities were evaluated by the Common Terminology Criteria for Adverse Events version 4.0. For all 78 patients, the 3-year LC and OS rates were 62% and 26%, respectively; they were 100% and 100%, respectively, in Group 1, and 76% and 40%, respectively, in Group 2. The 2-year LC and OS were 63% and 15%, respectively, in Group 3, and 62% and 16%, respectively, in Group 4. Overall response rate was 76% (complete response in 28 and partial response in 31). Grade 3 or higher acute toxicities, mainly hematological, were observed in 45% of the patients and 10% experienced grade 3-4 late toxicities. CRT with standard FP and 60-70 Gy of radiation appears to be tolerable for patients with esophageal cancer. Although outcome of this treatment in inoperable patients is not satisfactory, the 3-year LC of 100% for stage I patients and 76% for stage II-III operable patients appear promising. Further investigation is warranted to clarify the optimal radiation dose in CRT for esophageal cancer.

Daily low-dose Cisplatin-based concurrent chemoradiotherapy for the treatment of cervical cancer in patients 70 years or older.

It has been established that concurrent chemoradiotherapy (CCRT) is efficacious for cervical cancer, but adherence is unsatisfactory among elderly patients. To improve adherence, we have developed and initiated a daily low-dose cisplatin-based CCRT regimen. Here, we retrospectively evaluated the use of CCRT, especially for elderly patients. The study included a total of 53 patients who were 70 years or older, had stage IB-IVA cervical cancer, and were initially treated with daily CCRT. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m(2) per day) and either low- or high-dose-rate intracavitary brachytherapy. The median age was 72 years (range, 70-85 years). The median follow-up duration was 32 months (range, 2-104 months). The 3-year overall survival rate was 79.0%. Daily cisplatin chemotherapy was successfully completed in 32 (60.4%) of the 53 patients. Grade 3 or 4 neutropenia was observed in 19 patients (36%). A late complication of grade 3 rectal hemorrhage occurred in 3 patients who received high-dose-rate brachytherapy. All primary tumors responded to daily CCRT; complete response was observed in 43 patients (91.5%) and partial response was observed in 4 patients (8.5%). Daily CCRT in patients 70 years and older had acceptable compliance and safety. Daily CCRT is suggested to be a good treatment option for elderly patients who have advanced cervical cancer and require concurrent cisplatin.

Phase II study of fosaprepitant +5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: A Hoosier Cancer Research Network Study.

e20737 Background: In our prior phase III study (J ClinOnc 30:3998-4003, 2012) the addition of aprepitant to 5-day cisplatin regimens for germ cell tumors showed a significant improvement in comple...

Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage.

Polyethyleneimine-polyethylene glycol (PEI-PEG), a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP) in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

Efficacy of aprepitant for nausea in patients with head and neck cancer receiving daily cisplatin therapy.

Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy). Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron (40 μg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80 mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days 1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimen except for aprepitant (control group). For efficacy endpoints based on nausea, the aprepitant group showed significantly better results, including a higher rate of complete response (no vomiting and no salvage therapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups with regard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adverse reactions to aprepitant. This study suggested that a triple antiemetic regimen containing aprepitant is safe and effective for HNC patients receiving daily cisplatin therapy.

Une forme rare de lymphome cutané primitif

Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab.Patients received high dose accelerated radiotherapy (66 Gy in 24 fractions) and concurrent daily Cisplatin (6 mg/m2) without (Arm A) or with (Arm B) weekly Cetuximab (400 mg/m2 loading dose one week prior to radiotherapy followed by weekly 250 mg/m2). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6–8 weeks after treatment. Toxicity was reported as well.Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29 months. The OLCR was 84% in Arm A and 92% in Arm B (p = 0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p = 0.39; OS p = 0.99). Toxicity compared equally between both groups.The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity.

Additional weekly Cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: Efficacy and safety outcomes of a randomized, multi-center phase II study investigating

BackgroundModest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab. Patients and methodsPatients received high dose accelerated radiotherapy (66Gy in 24 fractions) and concurrent daily Cisplatin (6mg/m2) without (Arm A) or with (Arm B) weekly Cetuximab (400mg/m2 loading dose one week prior to radiotherapy followed by weekly 250mg/m2). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6–8weeks after treatment. Toxicity was reported as well. ResultsBetween February 2009 and May 2011, 102 patients were randomized. Median follow up was 29months. The OLCR was 84% in Arm A and 92% in Arm B (p=0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p=0.39; OS p=0.99). Toxicity compared equally between both groups. ConclusionThe addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity.

Concurrent chemoradiotherapy with low-dose daily cisplatin for high risk uterine cervical cancer: a long-term follow-up study

ObjectiveTo evaluate the clinical efficacy of concurrent chemoradiotherapy (CCRT) using daily low-dose cisplatin for cervical cancer.MethodsFifty-one patients with locally advanced cervical cancer (FIGO stage IB2, bulky IIA, IIB-IVA) who were treated with CCRT as primary therapy at Kurume University Hospital between 2000 and 2007 were retrospectively reviewed. CCRT consisted of 5 mg/m2/day of cisplatin 5 days per week, and external beam radiotherapy (EBRT) administrated to whole pelvis to 45-50.6 Gy. High-dose-rate intracavitary brachytherapy was delivered in a single dose of 4-5 Gy at point A, once a week after 20-30 Gy of EBRT.ResultsThe median follow-up duration was 42 months (range, 5 to 116 months). The overall response rate was 94.1%. Five year overall survival rate was 71.5% and 46.2% in stage I or II, and stage III or IVA, respectively. During follow-up period, 30 recurrences (58.8%) were found, the local failure rate was 39%, and distant failure rate was 35.2%, and both (local and distant) were 15.7%. Hematological toxicities were the most frequent acute toxicities. Grade 3 and 4 neutropenia was observed in 37.3%. Late intestinal toxicities appeared in 7 cases (13.7%), which occurred between 6 and 114 months after treatment. Four cases required bowel surgery.ConclusionCCRT using daily low-dose cisplatin was tolerable and showed favorable initial response as the primary therapy for locally advanced uterine cervical cancer. But there was no remarkable long-term benefit for patients' survival or local disease control in this study. The incidence of late intestinal toxicity still requires further investigation.