Cisplatin Infusion Research Articles

Superselective Intra-arterial Cisplatin Infusion with Concomitant Radiation Therapy for Base of Tongue Cancer

Superselective Intra-arterial Cisplatin Infusion with Concomitant Radiation Therapy for Base of Tongue Cancer

Treatment of Uterine Sarcoma with rAd-p53 (Gendicine) Followed by Chemotherapy: Clinical Study of TP53 Gene Therapy.

This study evaluated the efficacy of rAd-p53 (Gendicine®) followed by chemotherapy for the treatment of uterine sarcoma. Twelve cases of uterine sarcoma treated at Shengjing Hospital were retrospectively analyzed. Among the 12 patients, one had primary cancer, and 11 had recurrent cancer. For the recurrent cases, the interval between the first operation and diagnosis of recurrence, or progression-free survival time 1 (PFS1), was 1-18 months (median 3 months). All patients were treated with local application of rAd-p53 followed by chemotherapy (local injection of bleomycin and i.v. infusion of cisplatin, epirubicin, and isocyclophosphamide). Efficacy was evaluated, and the rates of complete remission (CR) and partial remission (PR) were calculated. During follow-up, PFS time 2 (PFS2) after the baseline period and overall survival (OS) time after the baseline period of rAd-p53 treatment data were obtained. The treatment resulted in one CR, seven PR, three with stable disease (SD), and one with progressive disease (PD). The remission rate (CR + PR) was 66.7%, and the responsive (CR + PR + SD) rate was 91.7%. PFS2 ranged from 2 to 62 months, with a median of 13 months, which is 10 months longer than that of PFS1; this difference was statistically significant (p = 0.0038). The OS time ranged from 6 to 62 months, with a median of 24 months. Following the combined treatment, four of the patients underwent a second debulking surgery. Of the two patients with liver metastases, one had CR of liver foci, and one had PR. Up to the follow-up date of the two patients who survived, one was tumor-free for 60 months. The PFS2 for the other patient was 39 months. This patient survived with tumor for 53 months with slow disease progression. The remaining 10 patients died. Local application of rAd-p53 combined with local injection of bleomycin and intravenous infusion of cisplatin, epirubicin and isocyclophosphamide was effective for treatment of uterine sarcoma, especially for patients with liver metastases. For patients with uterine sarcoma who do not have the opportunity for surgery, this regimen can be used as a new adjuvant therapy to obtain a surgical opportunity that allows further debulking of the tumor mass.

Сombined radiotherapy for cervical cancer with the use of polyradiosensitization with cisplatin and gemcitabine - immediate trial results of Azerbaijan national center of oncology

Aim. Study of immediate results of chemoradiotherapy of locally advanced cervical cancer with the use of polyradiosensitization with cisplatin and gemcitabine. Methods. The article analyzes diagnostic and treatment results of 128 patients with IIA-IIIB stage cervical cancer. The age of patients varied between 31 and 76 years. External beam radiotherapy was performed with 1.8 Gy fraction up to a total dose of 45 Gy, high dose rate brachytherapy consisted of four 7.0 Gy fractions. Patients from group 1 received weekly infusions of cisplatin (40 mg/m2) and from group 2 - polyradiosensitization with cisplatin (40 mg/m2) and gemcitabine (75 mg/m2). Results. Chemoradiotherapy with the use of polyradiosensitization compared to standard chemoradiotherapy allowed significant improving of immediate results of treatment of patients with locally advanced cervical cancer, which was particularly prominent in such unfavorable cases as cervical adenocarcinoma and IIIB stage of the disease. Early toxicity of the treatment was higher in group 2 but effectively resolved with symptomatic supportive treatment and did not lead to interruptions in radiotherapy. Conclusion. Combination of conformal external beam radiotherapy, high dose rate intracavitary brachytherapy and concurrent polychemotherapy with cisplatin and gemcitabine is feasible and reasonably safe; chemoradiotherapy with the use of polyradiosensitization improves immediate results of the treatment of cervical cancer with acceptable level of toxicity.

Tolerance of Chemoradiation in Advanced Head and Neck Cancers: Comparison Between Inpatients and Outpatients.

Concurrent chemoradiation (CCRT) is the mainstay of treatment for majority of locally advanced head and neck carcinomas (LAHNC). Addition of chemotherapy to radiotherapy increases the probability of local control and improved disease-free survival but at the cost of acute and delayed toxicities. A retrospective observational study. To compare the tolerance of CCRT and its toxicity profile amongst two groups, first arm (Arm A) being outdoor patients and the second group (Arm B) was hospitalized patients of LAHNC in an oncology centre of a tertiary care hospital. A total of 100 patients were enrolled, 50 in each arm. Overall, the most common site was oropharynx, followed by larynx and hypopharynx. 38 patients in Arm A received full 6 cycles of weekly chemotherapy with Inj Cisplatin infusion. 39 of the hospitalized patients completed 6 cycles of weekly Cisplatin, 04 patients also received 3 weekly Cisplatin. Average duration of treatment was 49.18days in arm A and 50.92days in arm B. Incidence of Grade II onwards dysphagia was 48 and 45 (96 and 90%) in Arm A and Arm B respectively; Chi Square value-0.6 (Yate's corrected); P value-0.43. Grade III oral mucositis was seen in 14% patients in Arm A and 34% patients in Arm B. 3 patients (6%) in Arm A and 14 patients (28%) in Arm B has Grade II and III hematological toxicities and nephrological toxicities. Aspiration pneumonia was seen in 2 patients (4%) in Arm A and in 4 patients (8%) in Arm B, Chi Square value-0.2 (Yate's corrected) P value-0.67. The incidence of febrile neutropenia was 3 and 10 in Arms A and B (6 and 20%) respectively. The tolerance of CCRT in hospitalized patients is marginally better, with relatively few associated complications as compared to outdoor setting. Every institute should promulgate its own guidelines regarding hospitalization of such patients.

Treatment Outcomes of Radiation Therapy Combined with Superselective Intra-arterial Infusion Therapy for Maxillary Sinus Cancer

The purpose of this retrospective study is to evaluate the efficacy of radiotherapy combined with superselective intra-arterial infusion therapy of cisplatin for locally advanced maxillary sinus cancer at single institution. We have evaluated 38 patients with locally advanced maxillary sinus cancer, who were treated with curative intent radiotherapy combined with superselective intra-arterial infusion therapy of cisplatin from 2002 to 2016. There were 31 males and 7 females. The median age was 67.5 years (range 47 to 87 years). Stage distribution was T2 in 1 case, T3 in 5 cases, T4a in 23 cases, and T4b in 9 cases. All patients have no nodal involvement. There were 36 patients who had squamous cell carcinomas, and 2 with undifferentiated carcinomas. Thirty-five patients received three-dimensional conventional radiotherapy, and the 3 most recent patients received intensity-modulated radiation therapy. We used 4 MV and/or 10 MV X-ray with or without electron beams. Median prescribed dose was 66 Gy (range 50 to 70 Gy) in 2 Gy/fraction. All patients did not receive either prophylactic neck irradiation or volume reduction surgery before radiotherapy. Superselective intra-arterial infusions of high-dose cisplatin was performed in 36 patients with simultaneous intra-venous infusions of thiosulfate to neutralize cisplatin toxicity, and 2 patients received selective intra-arterial infusion chemotherapy without sodium thiosulfate neutralization. All patients were treated with median 6 cycles (range 2 to 10 cycles) of intra-arterial infusion chemotherapy per week during radiotherapy. Systemic chemotherapy was also combined in 2 patients after the completion of radiotherapy. The median follow-up period was 38.9 months (range 3.6 to 178.3 months). The 5-year overall survival rate, disease-free survival rate, and local progression-free survival rate were 78.3% (T2-3/T4:100%/70.4%), 44.5% (T2-3/T4:83.3%/36.0%) and 58.3% (T2-3/T4:83.3%/53.7%), respectively. Although 13 patients had persistence of disease, delayed local failure occurred only in 2, regional recurrence in 3, and distant metastasis in 4. As salvage treatment, 9 patients underwent salvage surgery, and 2 patients underwent stereotactic radiotherapy. Although acute Grade 3 mucositis developed in 10 patients, no renal dysfunction occurred during the treatment. There were 9 late complications, including osteonecrosis (2 patients), carotid cavernous sinus fistula (1 patient), cateract (2 patients), blindness (4 patients) as late adverse reactions. Radiotherapy combined with superselective intra-arterial infusion therapy of cisplatin for maxillary sinus cancer appears to be efficient. However, further work is needed to decrease late complications.

Preliminary Treatment Results of Radiation Therapy With Intra-Arterial Infusion Chemotherapy for Oral Cancer

We retrospectively evaluated the efficacy and safety of radiotherapy with intra-arterial infusion chemotherapy for oral cancer. Between June 2013 and February 2016, 19 patients with previously untreated oral cancer were treated with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulphate. Sixteen of the 19 cases were treated with systemic chemotherapy. There were 10 males and 9 females. The median age was 61 years (range, 31-77). The primary sites were the oral tongue (n=15, 79%), gingival (n=2, 11%), buccal mucosa (n=1, 5.3%), and floor of mouth (n=1, 5.3%). The clinical stages were II (n=2, 11%), III (n=1, 5.3%), IVA (n=15, 79%), and IVB (n=1, 5,3%). Most patients (n=17, 89%) were treated with more than 5 cycles of intra-arterial infusion chemotherapy with cisplatin (20-50 mg/m2, median total dose: 50 mg/m2). The median irradiation dose was 70 Gy/35 fractions. The median follow-up period was 23 months (range: 8-44 months). The 2-year overall survival, progression-free survival, and local control rate were 87%, 72%, and 94%respectively. One patients experienced local failure, three experienced regional failure, and two developed distant metastasis. Major acute toxicities of more than grade 3 were oral mucositis in 10 (53%) patients. There were no neurological complications. Radiotherapy with intra-arterial infusion chemotherapy for oral cancer is effective and safe.

Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil versus transarterial chemoembolization using doxorubicin for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective analysis.

Background:More than one-third of hepatocellular carcinoma (HCC) patients are diagnosed at advanced stage with portal vein tumor thrombosis (PVTT) or extrahepatic metastasis. However, the outcomes of current therapeutic approaches are unsatisfactory. As a novel therapeutic strategy for unresectable HCC with PVTT, we analyzed the outcomes of transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (TAC-ECF) and compared its therapeutic effects and toxicity with transarterial chemoembolization (TACE) using doxorubicin (DOX).Methods:A total of 540 consecutive HCC patients who received TACE at the Catholic Medical Center between January 2007 and November 2013 were enrolled. Of these patients, we retrospectively analyzed 129 Barcelona clinic liver cancer stage C HCC patients with PVTT who received either TAC-ECF or TACE using DOX.Results:The objective tumor response rate was higher in the TAC-ECF group, with 31.3% objective response rate after TAC-ECF compared to 10% after DOX treatment (p = 0.004). Median follow-up period was 7 months (range, 1–57 months). The overall survival rate was also significantly higher in the TAC-ECF group compared to the DOX group (median 9.3 versus 4.6 months, p < 0.0001). Multivariate analysis revealed that TAC-ECF and extrahepatic metastasis were independent predictive factors for overall survival (p < 0.0001 and p = 0.002 respectively). No serious adverse effects developed in both groups.Conclusions:TAC-ECF therapy was tolerable and showed higher overall survival rate and tumor response compared to the conventional TACE DOX in advanced stage HCC patients with PVTT. Therefore, TAC-ECF may be considered as an effective treatment option for patients with unresectable HCC.

Cisplatin-induced human peripheral blood mononuclear cells' oxidative stress and nephrotoxicity in head and neck cancer patients: the influence of hydrogen peroxide.

Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX™Red, H2DCF-DA, and Amplex® Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O 2•- ), hydrogen peroxide (H2O2), and general reactive oxygen species production occurred. A higher production of H2O2 was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between H2O2 production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5days following cisplatin administration. In conclusion, H2O2 production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.

Osteoradionecrosis of the hyoid bone after intra-arterial chemoradiotherapy for oropharyngeal cancer: MR imaging findings

BackgroundOsteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone.MethodsThe study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis.ResultsA total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone.ConclusionOur MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

Abstract 2757: Using liquid biopsies and NGS as tools to analyze mutation burden and copy number variation in the blood of a patient with triple negative breast cancer to better inform therapeutic targets

Abstract The ability to characterize molecular features of cancer from liquid biopsies is resulting in the development of innovative health care for patients. Longitudinal changes in the mutational profiles of DNA isolated from liquid biopsies are being used to better understand and monitor the development, progression, and evolution of therapy resistance in cancer patients. To define changes in the mutational landscape and predict drug susceptibilities in Triple Negative Breast Cancer (TNBC) patients, we used whole exome analysis to profile circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) from eight selected time points of a patient enrolled in the Intensive Trial of OMics in Cancer clinical Trial (ITOMIC-001). The patient initially received weekly cisplatin infusions followed by additional targeted therapy. Peripheral blood samples were collected at specific time points over a period of 272 days following enrollment in the clinical trial. Our data indicates that the identified mutations in genomic DNA isolated from CTCs and ctDNA can be used to understand and mitigate the impact of tumor heterogeneity in addition to identifying clinically relevant mutations at these selected time points. To further increase the resolution of our analysis, we profiled ctDNA from these samples to a higher depth targeting only clinically relevant genes. These analyses increased the sensitivity of detection and identified additional targets that could have been used for therapeutic intervention. In addition to sequence variants, copy number variations (CNVs) have also been significantly associated with the development of metastasis and changes in CNVs have been used to monitor disease progression. We performed a bioinformatics analysis of genomic instability and CNVs across 32 different time points from ctDNA from the same patient throughout the treatment period. The genomic instability number (GIN) calculated for each of the 32 time points seems to mirror the overall CTC burden in the patient at each time point tested. CNV analysis is ongoing and these data sets are being further analyzed in combination with TCGA data to define possible cancer driver genes for the functional prediction of significant TNBC candidate alterations and the results of these analyses will be presented. Citation Format: Kellie Howard, Kimberly Kruse, Brianna Greenwood, Elliott Swanson, Mathias Ehrich, Christopher K. Ellison, Taylor Jensen, Sharon Austin, Arturo Ramirez, Debbie Boles, John Pruitt, Elisabeth Mahen, Jackie L. Stilwell, Eric P. Kaldjian, Michael Dorschner, Sibel Blau, Marcia Eisenberg, Steve Anderson, Anup Madan. Using liquid biopsies and NGS as tools to analyze mutation burden and copy number variation in the blood of a patient with triple negative breast cancer to better inform therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2757. doi:10.1158/1538-7445.AM2017-2757

Bolus infusion of cisplatin, 5-fluorouracil, and leucovorin as alternative first-line therapy for advanced gastric cancer.

e15511 Background: Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide.Classic regimens in first line setting for advanced GC combine platinum compounds and fluoropirimidines ± antracyclines or docetaxel. At Brazilian National cancer Institute (INCA), there are limitations in hospital beds and infusion pumps, so the combination between cisplatin (CDDP) + 5-Fluorouracil (5-FU) in an infusion protocol has been out of possibility. An institutional project with an adapted protocol involving CDDP + 5-FU + Leucovorin (CFL) in bolus demonstrated good results and CFL became routine at INCA for more than 10 years. Methods: Retrospective cohort study evaluating 109 patients with advanced GC treated in first line setting with CDDP 80mg/m2(D1) + 5- FU 400mg/m2 (D1,D8,D15,D22)+ Leucovorin (LV) 20mg/m2 (D1,D8,D15,D22) in 28-day cycles from January 2008 to December 2014. Results: The median age was 54 years (24y-80y), 53.6% were male, 70% white and 20% mulatto, 49.1% formal smokers and 15.5% formal drinkers. Tumor staging at initial diagnosis was: E IIA 2.7%, E IIB 2.7%, E IIIA 1.8%, E IIIB 5.5%, E IIIC 5.5% and E IV 81.8%. Performance status ≤ 2 was present in 97.3% and G3 disease in 63.6%. The most common metastatic sites were: lymph nodes 31.8%, peritoneum 24.5%, liver 21.8% and lung 2.7%. The median of cycles received per patient was 4. Complete responses were achieved in 6.4%, partial responses in 14.5% and stable disease in 14.5%. Median PFS was 6.3 months (5.08 – 7.58) and median OS was 8.3 months (6.79 – 9.87). Seventy five (68.8%) patients were alive in 1-year and 26 (23.9%) in 2-years. Dose reduction was necessary in 9.1% and the most common toxicities were: nausea 27.3%, vomiting 19.3% fatigue 13.6%, diarrhea 10.6%, mucositis 4.2% and neutropenia 4.2%. Of all adverse events, grade 3 and 4 corresponded to 11.36% and 1.51%, respectively. Three patients had neutropenia G4. Only 26 patients (23.8%) received second line treatment. Conclusions: Chemotherapy protocol in bolus combining CDDP, 5-FU and LV could be an alternative for CDDP and 5-FU infusion protocol.

Chemotherapy for primary mediastinal yolk sac tumor in a patient undergoing chronic hemodialysis: a case report

BackgroundThe safety and efficacy of chemotherapy for patients undergoing concomitant hemodialysis have not been fully established and optimal doses of anti-cancer drugs and best timing of hemodialysis remains unclear. Although chemosensitive cancers, such as germ cell tumors, treated with chemotherapy should have sufficient dose intensity maintained to achieve the desired effect, many patients with cancer undergoing hemodialysis might be under-treated because the pharmacokinetics of anti-cancer drugs in such patients remains unknown.Case presentationWe describe a 31-year-old Japanese man with a mediastinal yolk sac tumor treated with surgery followed by five cycles of chemotherapy containing cisplatin and etoposide while concomitantly undergoing hemodialysis. The doses of these agents used in the first cycle were 50% of the standard dose of cisplatin (10 mg/m2) and 60% of the standard dose of etoposide (60 mg/m2) on days 1 through to 5; the doses were subsequently escalated to 75% with both agents. Hemodialysis was started 1 hour after infusions of these agents. Severe hematological toxicities were observed despite successful treatment. During treatment with concurrent hemodialysis, pharmacokinetic analysis of cisplatin was performed and its relationship with adverse effects was assessed. Compared with patients with normal renal function, the maximum drug concentration was higher, and concentration increased in the interval between hemodialysis and the subsequent cisplatin infusion, resulting in a higher area under the curve despite a reduction in the dose to 75% of the standard regimen.ConclusionsBecause of the altered pharmacokinetics pharmacodynamics status of patients with renal dysfunction undergoing hemodialysis, pharmacokinetics pharmacodynamics analysis is deemed to be helpful for effective and safe management of chemotherapy in patients undergoing hemodialysis.

Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity.

The success of cisplatin-containing regimens to treat solid tumors is limited, in part, by nephrotoxicity. In rodents, several urinary proteins have emerged that are sensitive indicators of cisplatin-induced kidney injury. We sought to characterize time-dependent changes in the urinary concentrations of 12 proteins, including kidney injury molecule-1 (KIM-1), calbindin, beta 2-microglobulin (β2M), and trefoil factor 3 (TFF3) after cisplatin therapy. Urine was collected at baseline, 3 days (range, 2-5 days), and 10 days (range, 9-11 days) from 57 patients with solid tumors receiving outpatient cisplatin therapy (≥25 mg/m2 ). Serum creatinine was largely unchanged after cisplatin infusion. However, compared with baseline values, several novel biomarkers were significantly increased in the urine, including β2M, which was threefold higher by day 3 (P < 0.0001). Urinary KIM-1 and TFF3 were elevated twofold by day 10 (P = 0.002 and P = 0.002, respectively), whereas calbindin levels were increased eightfold (P < 0.0001). We report novel time-dependent changes in the urinary excretion of noninvasive markers of subclinical kidney injury after cisplatin treatment.

FRI-068 - Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-FU for advanced hepatocellular carcinoma refractory to conventional transarterial Infusion with doxorubicin

FRI-068 - Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-FU for advanced hepatocellular carcinoma refractory to conventional transarterial Infusion with doxorubicin

上顎洞癌に対するシスプラチンの超選択的動注と放射線治療の同時併用療法

上顎洞癌に対するシスプラチンの超選択的動注と放射線治療の同時併用療法

Acute Tumor Lysis Syndrome after Cisplatin and Gemcitabine for Treatment of Urothelial Carcinoma of the Renal Pelvis: Case Report and Review of Literature

Tumor lysis syndrome (TLS) is a potentially fatal complication of oncological therapy. It is rarely described in patients with solid tumors, even rare in urological cancer. To the best of our knowledge, there were only two cases describing TLS following chemotherapy for metastatic urothelial carcinoma documented in the literature, although only one occurred after gemcitabine, another case occurred after PD-1 Immunotherapy. Case presentation: We present the case of a 67-year-old female who developed acute renal failure and tumor lysis syndrome after a single infusion of cisplatin and gemcitabine for metastatic renal pelvic urothelial carcinoma. Conclusions: Patients with urothelial carcinoma that are highly proliferative and have high tumor burden are at high risk of developing hyperuricemia and TLS, while undergoing chemotherapy. Although TLS is rare in solid tumor, oncologists should be alert when treating patients at high risk of TLS, and determine appropriate prophylaxis. We also proposed biomarker based risk stratification for patients with high risk for TLS.

Impact of induction chemotherapy to concurrent chemoirradiation over radiotherapy alone in advanced oral cavity.

Oral and oropharyngeal carcinomas representing about 90% of all oral malignancies are the sixth most common cancers worldwide. Basic modalities of cancer treatment are surgery, radiotherapy, and chemotherapy (CT) either alone or in combination. For squamous cell carcinoma (SCC) patients, induction CT followed by radiotherapy and concurrent CT are effective methods for improving response rates. Fifty patients with advance stage oral cavity cancer with performance status >60% on Karnofsky performance scale and having no prior exposure to CT, radiotherapy, and surgery were included in the study. CT including bleomycin, methotrexate, and cisplatin was given on day 1 and repeated at an interval of 21 days. After the completion of three cycles, two groups (n = 25 each) were formed. One group was treated with radiotherapy alone and other group of patients treated with radiotherapy and concurrent cisplatin infusion. The patient toxicities and response were evaluated. After completion of induction CT, both the groups responded with almost similar result. Nausea, vomiting, mucositis, and skin reactions during radiotherapy were observed in both groups but comparatively higher in Group "B." In Group B, 84% (vs. 60% in Group A) of patients showed complete response (CR) after completion of treatment, and out of 13 patients who responded partially to induction CT, 9 patients showed CR after concurrent chemoradiotherapy. This study showed the superiority of induction followed by concurrent chemoradiotherapy over induction plus radiotherapy alone in the treatment of advanced oral cavity neck SCC.

Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: A Prospective Observational Cohort Study.

Background:Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited.Objective:To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension).Design:This is a 3-year observational prospective cohort study.Setting:The study includes 12 Canadian pediatric oncology centers.Patients:The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin.Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 or a pre-existing renal transplantation at baseline.Measurements:Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected.Methods:Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines.Procedure: Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes).Limitations:The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved.Conclusions:ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs.

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial

Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. US National Cancer Institute.

1012P - A multi-institutional dose-finding and efficacy confirmation trial of superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for patients with locally advanced maxillary sinus cancer (JCOG1212, RADPLAT-MSC): Results of dose-finding phase

Superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT) has been performed for the patients with locally advanced maxillary sinus squamous cell carcinomas (LA-MSSCCs) in several institutions and has been reported to result in a favorable survival. This multi-institutional prospective trial was aimed to confirm the adequate dose and efficacy of RADPLAT for the patients with LA-MSSCCs. The dose-finding phase was performed to evaluate the incidence of dose-limiting toxicity (DLT) and to determine the recommended cycle of intra-arterial infusion of cisplatin. Eighteen patients were registered from 7 institutions for this study. In this dose-finding study, 100 mg/m2 of cisplatin was administered intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy). Cisplatin was skipped in the case of adverse events that met the skipping rule defined by the protocol. The recommended number of cycles was determined according to the distribution of the number of cycles of administered cisplatin and the incidence of DLT. The median age of all participants was 64 years old (range, 40-75 years old). Sixteen patients were diagnosed as T4aN0M0, and two patients as T4bN0M0. All patients achieved full dose of radiotherapy. The number of cycles of administered cisplatin was 7 in 13 patients and 6 in 5. DLT was observed in 5 patients; Gr 3 liver dysfunction (1), Gr 4 thrombocytopenia (1), Ccr < 40 (1), Gr 3 retinopathy (1), and Gr 3 retinal detachment (1). There was not either treatment-related death or neural complication. RADPLAT appears to be safe and well-tolerated at 7 cycles of cisplatin at a dose of 100 mg/m2 each cycle, which were determined to be the recommended number of cycles for LA-MSSCC.