Cisplatin Infusion Research Articles

Phase I study of weekly docetaxel and cisplatin arterial infusion for recurrent head and neck cancer

We planned a phase I study of weekly arterial infusion of docetaxel and cisplatin via a superficial temporal artery for recurrent head and neck cancer to determine the optimal dose. The dose of cisplatin was fixed and the dose of docetaxel was escalated from 8 mg/m(2) , with an increase of 2 mg/m(2) per step, to identify the maximum tolerated dose (MTD). In total, 4 courses of weekly chemotherapy were administered. Twelve patients were recruited to this trial. The MTD of docetaxel was 14 mg/m(2) . At this dose level, dose-limiting toxicity was observed in 2 of 3 patients. One patient experienced grade 3 leukopenia, while the other experienced grade 3 leukopenia. Myelosuppression was the dose-limiting toxicity for this regimen. The recommended dose for weekly arterial infusion of docetaxel was identified as 12 mg/m(2) combined with weekly cisplatin at 40 mg/m(2) , with 4 courses of each.

Response to intra‐arterial cisplatin and concurrent radiotherapy in a patient with primary mucosal malignant melanoma of the nasal cavity

The prognosis for patients with mucosal malignant melanoma (MMM) of the nasal cavity is very poor because of the radioresistance of melanoma cells. We present the first case report of the efficacy of superselective intra-arterial cisplatin (CDDP) infusion concurrent with hypofractionated radiotherapy (RT) for MMM of the nasal cavity. A pink, polypoid mass, histopathologically diagnosed as an amelanostic melanoma, occupied the right nasal cavity. After the treatment, a nasal tumor disappeared, leaving only a small bulge in the medial wall of the middle turbinate. Histopathologic examination revealed scattered degenerated melanoma cells, remaining only in the small restricted area in the medial surface of the excised middle turbinate. Twelve months after the treatment, the patient has not experienced any local recurrence or regional and distant metastasis. The superselective intra-arterial CDDP infusion concurrent with hypofractionated RT might be useful for the management of nasal MMM.

Single‐arm phase II study of multiagent concurrent chemoradiotherapy and gefitinib in locoregionally advanced squamous cell carcinoma of the head and neck

This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC). Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m(2) /day and fluorouracil 1000 mg/m(2) /day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib. Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts. Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity.

Randomized, Phase II Study Comparing Interferon Combined with Hepatic Arterial Infusion of Fluorouracil plus Cisplatin and Fluorouracil Alone in Patients with Advanced Hepatocellular Carcinoma

Objective: This randomized phase II trial compared the response rates to treatment with interferon (IFN) combined with hepatic arterial infusion of fluorouracil (FU) plus cisplatin (CDDP) or FU alone in patients with advanced hepatocellular carcinoma (HCC). Methods: A total of 114 patients with measurable advanced HCC were enrolled and randomized into 2 groups. FU (300 mg/m², days 1–5, days 8–12) with or without CDDP (20 mg/m², days 1 and 8) was administered via the hepatic artery. IFNα-2b was administered 3 times per week for 4 weeks. Results: The response rates were 45.6% for the IFN/FU + CDDP group and 24.6% for the IFN/FU group. The response rate was significantly higher in the IFN/FU + CDDP group (p = 0.030). The median overall survival period was 17.6 months in the IFN/FU + CDDP group versus 10.5 months in the IFN/FU group (p = 0.522). The median progression-free survival period was 6.5 months in the IFN/FU + CDDP group versus 3.3 months in the IFN/FU group (p = 0.0048). Hematological toxicity was common, but no toxicity-related deaths were observed. Conclusion: These results show the clinical efficacy of adding CDDP to the hepatic arterial infusion of FU in combined chemotherapy regimens with IFN.

Second Malignancies in Total Therapy 3 Trials for Newly Diagnosed Multiple Myeloma: Influence of Lenalidomide Versus Thalidomide in Maintenance Phases

Abstract 823 Background:Recent data from IFM, CALGB and GEMIMA trials suggest that utilizing lenalidomide as maintenance therapy is associated with a higher incidence of second cancers, including both hematologic and solid malignancies. Two successive Total Therapy 3 (TT3) trials, one employing as maintenance thalidomide (TT3A, n=303) and the other lenalidomide (TT3B, n=177), after tandem transplants offered the opportunity of investigating whether lenalidomide therapy was associated with greater probability of inducing second malignancies. Patients & Methods: The details of TT3A and TT3B trials and patient outcomes have been reported previously. Briefly, both employed identical induction therapy with 2 cycles of VTD-PACE (bortezomib, thalidomide, dexamethasone plus 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, etoposide), followed by melphalan 200mg/m2-based tandem autologous transplantation and 2 cycles of dose-reduced VTD-PACE consolidation. Maintenance consisted of VTD in the first year and TD for years 2 and 3 in TT3A, while TT3B employed VRD for all 3 years. All patients had signed an informed consent in keeping with institutional and federal guidelines. For the purpose of this analysis, the MM data base was interrogated for the development of CA-2 arising after protocol initiation and after start of maintenance therapy in TT3 trials. This was based on frequently scheduled positron emission tomography (PET) scanning, performed at baseline and on average every 3 months in the first year and semi-annually thereafter. For the early detection of potential MDS or AML, all bone marrow examinations included metaphase karyotyping and, when indicated because of pathological or clinical suspicion, inter-phase fluorescence in situ hybridization (FISH) for the detection of MDS- and AML- associated abnormalities. Chi-square and Fisher’s exact tests were used to compare baseline characteristics between protocols. Univariate and multivariate Cox proportional hazard regression were used to model associations between baseline covariates and onset of second malignancy. Furthermore, the Kaplan and Meier method was used to model cumulative incidence of second malignancy from the initiation of maintenance therapy. Results: TT3B patients had notably higher proportions of patients with ISS III disease and GEP70-high risk as compared to TT3A patients. There was an incidence of 16 new second primary cancers on TT3A over the entire period of observation with 7 solid tumors and 9 hematologic malignancies. We only observed 2 new second primaries on protocol TT3B (1 solid, 1 hematologic malignancy). There were no differences in cumulative incidence of hematologic CA2 or solid CA2 between the protocols from the initiation of maintenance therapy on the two TT3 trials (Figure 1). Cox regression analysis identified old age (> 66yrs) and high Kappa FLC levels (>168 mg/dl) as the only factors negatively associated with timing of onset of a second malignancy, when modeled from initiation of maintenance therapy. MDS associated cytogenetic abnormalities (MDS-CA) can occur as either transient or persistent anomalies on serial bone marrow analyses in post-transplant MM patients in absence of cytopenias or morphologic evidence of MDS, as previously reported. The 4-year incidence of MDS-CA in TT3B was significantly higher than TT3A. It remains to be seen whether such MDS-CAs progress to overt clinical MDS and therefore need to be followed prospectively. Conclusion: Our study has the great advantage containing large cohorts of patients who underwent treatment that only differed in the maintenance regimen. Furthermore we did not have to rely on multiple different methods of detecting incidental CA2 but rather obtained PET scans in regular intervals thus avoiding underreporting of CA2s. In terms of treatment our aproach can be best compared to the IFM 2005-02 and CALGB 100104 who both included HDT and HSCT. Overall we had a significant lower incidence of CA2 in the treatment arms than these comparable trials. Taken together, the data suggest that there are no discernable differences in CA-2 when combining different IMiDs with BZ/D as maintenance strategy. There is, however, a higher incidence of MDS karyotypic abnormalities, both transient and persistent, in patients who remain on the Bz/D/Len maintenance after having undergone autologous stem cell transplantation on TT3B. Disclosures:Barlogie:Celgene, Genzyme, Novartis, Millennium: Consultancy, Honoraria, Patents & Royalties.

Phase II Study of Carfilzomib (CFZ) Combined with Other Anti-Myeloma Agents in Relapsed-Refractory Multiple Myeloma (RRMM) - Updates on the UARK Compassionate Use Protocol

Abstract 2947 Background:CFZ is an epoxomicin derivative with ability to irreversibly inhibit proteosomes. It has been shown in preclinical and early clinical studies to have activity in newly diagnosed as well as RRMM. We have previously reported on the UARK compassionate use phase II study of CFZ which allowed for the addition of other anti-MM drugs in RRMM. We are now presenting data with 7 additional patients and longer follow-up, with data cut-off on August 9 2011. Methods: All patients with relapsed or resistant refractory multiple myeloma were eligible for the trial. First cycle CFZ was given at 20mg/m2 IV day 1, 2, then 27mg/m2 IV days 8, 9, 15, 16 every 28 days; 4mg of dexamethasone (DEX) was given with each CFZ dose. In the absence of at least PR, CFZ dose was escalated to 36 mg/m2 IV and DEX increased to 20mg. Additional anti-myeloma drugs were added Cycle 2 onwards in absence of PR. 16-day continuous infusion cisplatin (3–5 mg/m2/d) and doxorubicin (1.5–3 mg/m2/d) were commonly added from Cycle 2 onwards, along with other novel agents. Cox regression modeling was employed for overall survival (OS) and progression free survival (PFS). Results: 81 patients with RRMM were enrolled. Baseline characteristics included age >=65yr in 32%, ISS stage >=II was seen in 72% of patients, cytogenetic abnormalities (CA) in 68%, and GEP-defined high risk in 53% of patients. 77 patients had prior autologous stem cell transplant. 63 patients (78%) had at least 2 transplants. All 81 patients had received regimens containing bortezomib, thalidomide, lenalidomide, melphalan or steroids. At least 1 cycle of treatment was administered to all 81 patients enrolled, 69% of patients received >1 cycle of treatment and only 19% received >5 cycles. 71 patients (88%) discontinued therapy primarily due to progression, death or toxicity. 5% patients achieved nCR/CR/sCR, additional 19% patients had stable disease. OS benefit was observed in patients receiving >= cycle 3 (HR= 0.40, p=0.006) on univariate analysis and multivariate analysis (HR=0.09, p<0.001) with adjustment for GEP-defined risk status. Most common toxicities, counting all toxicities (>=grade 3) were thrombocytopenia (84%), anemia (77%), leukopenia (73%), hypophosphatemia (58%), hypokalemia (27%) and fatigue (25%). Grade 1–2 peripheral neuropathy (PN) was present at baseline in 53%, >grade 3 PN was observed in 7% (6/81) after cycle 1, whereas >grade 3 PN was observed in 8% (1/12) >5 cycles.OS and PFS at 12 months were 41% and 5%, respectively (Figure 1). Conclusions: The data presented herein, confirm and extend the previously reported results on CFZ demonstrating anti-myeloma activity and clinical benefit, alone and in combination with other agents, in our heavily pre-treated RRMM population. Surprisingly, worsening or new PN was not observed in majority of patients. Utilizing the novel proteasome inhibitor CFZ in combination with other anti-MM agents on a compassionate basis afforded us the opportunity to make observations regarding potential clinical synergy of particular combinations. In particular, combination of CFZ-DEX with lenalidomide and vorinostat has shown promise in a subset of RRMM patients. [Display omitted] Disclosures:Barlogie:Celgene: Consultancy, Honoraria, Research Funding; IMF: Consultancy, Honoraria; MMRF: Consultancy; Millennium: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy; Novartis: Research Funding; NCI: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding.

Combined modality therapy for laryngeal cancer with superselective intra-arterial cisplatin infusion and concomitant radiotherapy

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.

Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin

Cisplatin has shown a high tumor response rate among head and neck carcinomas, and the tumor response is related to the cisplatin dosage. The purpose of this study was to evaluate the efficacy and toxicity of selective intraarterial chemoradiation therapy for oropharyngeal carcinomas with high-dose cisplatin. This retrospective study consisted of 21 patients with oropharyngeal carcinoma, stages II-IVB, in whom intraarterial chemoradiation therapy was performed between 2000 and 2008. All patients were given two courses of selective intraarterial infusions of cisplatin (300 mg/m(2)), systemic chemotherapy with 5-fluorouracil, and simultaneous radiation therapy (58-61 Gy/30 fractions), with a 1-week rest period. The 2-year overall survival rate of the 15 patients who completed the therapeutic regimen was 71.3%. The 2-year locoregional control rate and disease-free survival rate were 95.0% and 67.7%, respectively. Selective intraarterial high-dose cisplatin chemotherapy with concomitant radiation therapy shows results similar to those of original methods in terms of survival and locoregional control with a reduction in the number of procedure times.

An Integrated In Vitro and In Vivo High-Throughput Screen Identifies Treatment Leads for Ependymoma

Using a mouse model of ependymoma-a chemoresistant brain tumor-we combined multicell high-throughput screening (HTS), kinome-wide binding assays, and invivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both invitro and invivo, e.g., 5-fluorouracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation.

6585 POSTER Phase II Study of Low-dose Everolimus Plus Weekly Cisplatin and 24-hour Infusion of High-dose 5-fluorouracil and Leucovorin for First-line Treatment of Metastatic or Recurrent Gastric Cancers

the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin. Results: The hazard ratio for death in the capecitabine group was 0.88 (95% confidence interval [CI], 0.81 to 0.98) in comparison to fluorouracil and the hazard ratio for the oxaliplatin group was 0.93 (95%CI, 0.82 to 1.10) in comparison to cisplatin. Median survival times in the ECF, ECX, EOF, and EOX groups were 9.2 months, 9.3 months, 9.1 months, and 11.5 months, respectively; survival rates at 1 year were 36.6%, 38.9%, 40.1%, and 47.5%, respectively. Overall survival was longer with EOX than with ECF. Toxic effects of capecitabine and fluorouracil were almost similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity but with slightly higher incidences of neuropathy. Conclusions: In our experience, oxaliplatin and capecitabine are more effective than cisplatin and fluorouracil, respectively, in patients with previously untreated esophagogastric cancer.

局所進行食道癌に対するcisplatin単回投与, 5-fluorouracil 持続静注と放射線による術前複合療法

局所進行食道癌に対するcisplatin単回投与, 5-fluorouracil 持続静注と放射線による術前複合療法

Five‐year quality of life results of the randomized clinical phase III (RADPLAT) trial, comparing concomitant intra‐arterial versus intravenous chemoradiotherapy in locally advanced head and neck cancer

The purpose of this investigation was to present 5-years of quality-of-life (QOL) results of a multicenter randomized phase III trial, assessing intra-arterial (IA) versus standard intravenous (IV) chemoradiation for inoperable stage IV head and neck cancer. Evaluation of 71 patients through European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC QLQ-C30) and Head and Neck Module (QLQ-H&N35), and trial-specific questionnaires. Treatment consisted of standard radiotherapy with 4 weekly IA or 3 weekly IV cisplatin infusions. No significant differences in treatment-related QOL problems between 1 and 5 years posttreatment were observed, except for "dry mouth" (gradually improving; p = .004). Survivors have lower fatigue levels (p = .04), better voice (p = 0.3), and swallowing (p = .03) than patients who could not complete all subsequent follow-up questionnaires. Most treatment-related QOL issues deteriorate during treatment, improve in the first year, and then remain stable, except xerostomia, improving up to the 5-year assessment point. Survivors show more positive scores for fatigue, voice, and swallowing. QOL issues at 1 year, thus, for most already represent those after 5-year follow-up.

Survival and Long-term Outcomes in Children With Hepatoblastoma Treated With Continuous Infusion of Cisplatin and Doxorubicin

Despite high survival rates, many survivors of hepatoblastoma develop late effects including ototoxicity and cardiomyopathy. With the goal of minimizing long-term toxicities, our institution treated hepatoblastoma with continuous infusion of doxorubicin and cisplatinum (PLADO), rather than short infusion or bolus dosing as used in other treatment protocols. This retrospective cohort study includes consecutive patients diagnosed between 1985 and 2007. Patients were scheduled for treatment with 6 cycles of continuous infusion of PLADO with resection after the third or fourth cycle. Audiograms and echocardiograms were obtained at baseline, after every 2 chemotherapy cycles and yearly after the completion of therapy. Fifty-five patients were treated (34 localized; 21 metastatic). Fifty-one patients received at least 1 cycle of PLADO. Median follow-up was 7.0 years (range, 0.11 to 17.8 y). Event-free and overall survival for these 51 patients were 72.2% (standard error 6.3%) and 75.6% (standard error 6.2%) respectively. Of the 38 survivors treated with cisplatin who had an audiogram during follow-up, 4 (11%) demonstrated severe (Brock grade 3/4) and 13 (34%) mild (Brock grade 1/2) hearing loss. At a median of 10.0 years (range, 5.0 to 13.0 y) after therapy, 2 of 41 (5%) patients who were still alive had evidence of cardiac dysfunction. Overall, continuous infusion of PLADO therapy resulted in survival rates consistent with those observed in intergroup studies, but rates of chronic cardiac and ototoxicity did not differ sufficiently from those observed after shorter infusion of PLADO therapy to warrant the use of continuous infusions.

A prospective study of predictive factors for chemotherapy-induced nausea and vomiting.

e19720 Background: Despite effective antiemetics, patients (pts) still develop nausea and vomiting after chemotherapy. While the emetogenic potential of different chemotherapy drugs has been established, the contributing patient and disease factors are less understood, and are the subject of this prospective study. Methods: Cleveland Clinic (CC), pts with locoregionally advanced, non-metastatic cancer of the head and neck (HN), esophagus, and gastro-esophageal junction (E/GEJ) are frequently treated in the hospital with concurrent chemoradiation using 96 hour infusions of cisplatin (20 mg/m2/day) and 5FU (1000 mg/m2/day). Between 7/09 and 9/10, all pts receiving their first course of chemotherapy with this regimen were entered in this study. A standard antiemetic prophylactic and therapeutic algorithm was utilized. Demographics, disease characteristics, potential risk factors, and maximum CTCAE v3.0 grade nausea and vomiting were recorded. Logistic regression analysis was used to identify predictors for the primary endpoint of > grade 1 chemotherapy induced nausea and/or vomiting (CINV). Results: The study enrolled 120 consecutive pts; 87% were male, 90% white, 61 had HN cancer, and the median age was 57 (range 26-76) years. Alcohol use was moderate or heavy in 33% and pts lived a median 39 (range 4-3000) miles from the CC. Univariable predictors for CINV included limited (vs. moderate or heavy) alcohol use, greater distance from the CC, history of psychiatric disorder, and E/GEJ (vs. HN) cancer. Although a body mass index (BMI) <25 predicted for greater CINV than BMI >32, this was felt to reflect the chemotherapy dose reductions sometimes used in obese pts. On multivariable analysis, only limited alcohol intake (OR 2.64, 95% CI 1.12-6.22, P=0.026) and an E/GEJ primary (OR 3.53, 95% CI 1.50-8.31, P=0.004) proved predictive for CINV. Pts with HN cancer and moderate or heavy alcohol use had a 41% chance of CINV in contrast to an 86% chance of CINV in pts with E/GEJ cancer and limited alcohol. Conclusions: The importance of disease site in predicting for CINV in our series likely reflects the radiation therapy port used in this concurrent treatment. The only prospectively identified patient predictor for CINV was a limited alcohol intake.

Clinicopathologic features and treatment outcomes of patients (pts) with HER2-positive (pos) adenocarcinomas (ACA) of the esophagus (E) and gastroesophageal junction (GEJ).

4046 Background: HER2 is overexpressed in 21% of gastric and 33% of GEJ ACA, and pts with advanced HER2pos disease survive longer after chemotherapy and trastuzumab than after chemotherapy alone. This retrospective analysis was undertaken to better define the clinicopathologic features and treatment outcomes in pts with HER2pos ACA of the E and GEJ. Methods: Between 11/99 and 7/06, 156 pts with T3 or N1 or M1a ACA of the E or GEJ were entered on one of two Cleveland Clinic trials. Induction chemoradiation, with 96 hour infusions of cisplatin (20 mg/m2/d) and fluorouracil (1,000 mg/m2/d) beginning on day 1 of radiation (30 Gy at 1.5 Gy bid), was followed by surgery and identical post-operative chemoradiation. 76 pts also received 2 years of oral gefitinib. Pathology was tested for HER2 by immunohistochemistry using PATHWAY anti-HER-2/neu 4B5 Rabbit Monoclonal Primary Antibody (Ventana, Tucson AZ) and in situ hybridization with the INFORM HER2 Dual ISH DNA Probe Cocktail assay (Ventana, Tucson AZ). Baseline characteristics and outcomes after treatment of the HER2pos and negative (neg) pts were compared. Results: Of the 156 pts, 136 pts had either initial biopsy or resection specimen available. HER2 was deemed pos if either was pos. Discordance between biopsy and resection was found in only 6/65 pts (9%). 32 pts (24%) were HER2pos; 27% of 82 pts with GEJ, and 19% of 54 pts with E tumors (p=0.31). There was no statistical difference between HER2pos and neg pts in age, gender, race, stage, or pathological response. The only difference was that HER2neg tumors were more likely poorly differentiated (p<0.001). Locoregional control, distant metastatic control, freedom from recurrence and overall survival were statistically the same in both the entire cohort, and in the gefitinib-treated subset. Conclusions: Except for tumor differentiation, HER2pos and neg pts with ACA of the E and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2pos gastric cancer and the similar incidence of HER2 overexpression in the E and GEJ, further evaluation of HER2 directed therapy in this disease seems indicated.

Phase I study of sorafenib in combination with low-dose cisplatin and fluorouracil intra-arterial infusion chemotherapy.

e14563 Background: This study aimed to determine the recommended dose for combination therapy of sorafenib with hepatic arterial infusion of low dose cisplatin and fluorouracil in patients with adv...

Phase II trial of concurrent chemoradiotherapy consisting of two courses with S-1 and cisplatin for locally advanced esophageal cancer.

4034 Background: S-1 is a novel oral fluoropyrimidine anticancer agent designed to enhance clinical efficacy, reduce gastrointestinal toxicity, and enhance the effectiveness of radiotherapy. We conducted a phase II study of concurrent chemoradiotherapy with S-1 and cisplatin in patients with locally advanced esophageal cancer. Methods: Chemoradiotherapy consisted of two courses. The first course consisted of 30 Gy of radiotherapy given over 3 weeks plus daily treatment with oral S-1 (80 mg/m2/day) for 2 weeks and a 24-h infusion of cisplatin (70 mg/m2) on day 8. The second course of chemoradiotherapy was administered after 2 weeks. S-1 was administered in powdered form with water. Responders received at least two 4-week courses of chemotherapy with S-1 and cisplatin. Results: A total of 102 patients were enrolled (median age, 66 years; M/F, 88/14; PS 0/1, 77/25). Twelve patients had stage II disease, 61 had stage III disease, and 29 had stage IVa disease. Ninety-seven patients (95%) completed two courses of chemoradiotherapy. The most prominent toxicity was myelosuppression. Grades 3 and 4 leukopenia occurred in 37 (36%) and 14 (14%) patients, respectively. Nonhematological toxicity was moderate: grade 2 nausea, pain, oral mucositis, and renal dysfunction occurred in 31%, 29%, 20%, and 14% of the patients, respectively. These side effects resolved after one course of chemoradiotherapy in all but 7 patients. In patients with stage II disease, complete response (CR) and response rates (RRs) were 92% and 100%, respectively. In patients with stage III disease, CR and RRs were 64% and 85%. In patients with stage IVa disease, CR and RRs were 24% and 66%. All patients with stage II disease survived.Median survival time in patients with stage III disease was 795 days (95% CI: 589-1,038 days), and in patients with stage IVa disease, it was 369 days (95%CI: 194-523 days). Conclusions: Chemoradiotherapy consisting of two courses of S-1 and cisplatin was very effective with mild toxicity. We believe that this regimen can be one baseline treatment for patients with locally advanced esophageal cancer. Further trials in larger cohorts of patients are expected to strengthen the outcomes of this study.

Superselective arterial cisplatin infusion with concomitant radiation therapy for base of tongue cancer

The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success.

Comprehensive management of gallbladder cancer

Gallbladder cancer is the most common malignancy of biliary tract with a very poor prognosis. The therapeutic strategy of gallbladder cancer has been improved in some aspects. Identifying the accurate stage is the basis of surgical treatment. Radical resection is the only choice of treatment which provides patients long survival. For most patients in T1a stage, simple cholecystectomy is adequate, but dissection of hepatoduodenal ligament should be added when the lesions located in neck and duct of gallbladder. Patients in T1b stage often need radical cholecystectomy. Radical cholecystectomy with Ⅳb and Ⅴ segmentectomy and lymphadenectomy of N2 nodes should be performed to patients in T2 stage. Extended right lobe resection can improve the prognosis of selected T3 and T4 patients.The effect of chemotherapy for gallbladder cancer remains unsatisfactory, and current chemotherapeutic regimens were based on 5-FU, gemcitabine or S-1. The effect of a new chemotherapeutic sensitization scheme with continuous infusion of somatostatin,epirubicin 5-FU/CF and cisplatin is under research, and the preliminary results are promising. Radiation shows some benefits to patients with gallbladder cancer, but its effects are still uncertain. Key words: Gallbladder neoplasms; Surgical treatment; Chemotherapy; Radiotherapy

Abstract 4393: MRI-guided electroporation-mediated transarterial chemoembolization (E-TACE)

Abstract INTRODUCTION: Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability; electrochemotherapy (ECT) takes advantage of this phenomenon to increase tumor uptake of drugs. The purpose of this study was to demonstrate the potential to use MRI for intra-procedural optimization of an electroporation-mediated TACE (E-TACE) approach intended to increase liver tumor drug uptake compared to transcatheter infusion alone. MATERIALS &amp; METHODS: Eight New Zealand White rabbits were used for our ACUC-approved experiments. Two VX2 tumor portions were implanted in the left medial hepatic lobe of each rabbit and a total of fourteen VX2 tumors were grown in these rabbits. Two tumor were grown in 6 rabbits (one as E-TACE treated tumor and other as control) and solitary larger tumors was grown in 2 rabbits (half of tumor treated with E-TACE, remaining half as control). Each rabbit was catheterized under DSA guidance with catheter placed in the left hepatic artery. Next, Baseline transcatheter intraarterial perfusion (TRIP) MRI (1.5T, Siemens Medical) was performed to generate tumor enhancement curves with an intra-arterial (IA) injection of Gd-DTPA. These contrast enhancement curves were generated to estimate time delay between IA bolus infusion and the period of maximum tumor uptake (for planning purposes to optimize delay interval, Td, between later IA Cisplatin infusion and application of electrical pulses). For E-TACE treated tumors (one tumor in each rabbit) bi-polar electrodes (1cm spacing) were inserted straddling the targeted tumor and 8 100μs 1300V pulses applied at the selected delay interval Td after the administration of Cisplatin solution through the catheter. Next, a post TRIP-MRI scan was performed to assess tumor perfusion alterations and treatment related tumor signal intensity changes. After allowing 3 hours for Cisplatin wash out, rabbits were euthanized and each tumor sectioned for ICP-MS measurement of intra-tumoral platinum concentrations. RESULTS: ICP-MS results demonstrated significantly increased Cisplatin uptake in E-TACE treated tumors, increases of 6.0-fold compared to transcatheter infusion alone in six of the rabbits (n=6/8, p=0.017). Follow-up T2W-TSE images showed significant intra-tumoral T2W signal decreases in five rabbits (n=5/8) whereas no such signal changes were observed in other rabbits (two of which showed negligible Cisplatin uptake increases). CONCLUSION: Our findings suggest that E-TACE may be effective for increasing tumor uptake of chemotherapeutic agents and that intra-procedural MRI should permit immediate confirmation of targeted drug delivery based upon signal changes only present in sufficiently treated tissues. Additional longitudinal studies are required to evaluate and compare treatment response between animals treated with E-TACE and those treated with conventional TACE approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4393. doi:10.1158/1538-7445.AM2011-4393