Cisplatin Infusion Research Articles

Evaluation of the Role of Cisplatin-conjugated-soluble Gelatin Sponge: Feasibility Study in a Swine Model

To evaluate the safety and the delivery function of cisplatin-conjugated-soluble gelatin sponge in a swine model. Fifteen healthy young swine were assigned into three groups: transarterial cisplatin infusion group, transarterial chemoembolization (TACE) with cisplatin-conjugated 120-min soluble gelatin sponge (TACE-120) group, and TACE with cisplatin-conjugated 360-min soluble gelatin sponge (TACE-360) group. A total volume of 0.8 mL/kg cisplatin in each group and 8 mg/kg soluble gelatin sponge in TACE-120 and TACE-360 groups were injected from the left hepatic artery in small increments for 10 min. Common hepatic angiography and whole-blood sampling via the left hepatic vein were conducted to explore recanalization immediately after the procedure and again at 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min later. The area under the plasma concentration curve (AUC) of non-protein-bound platinum was compared among the three groups. Each liver was removed and cut into 10-cm-thick sections for calculating liver-damaged volume ratio. Sequential angiography depicted gradual recanalization of the occluded hepatic artery and total recanalization at 120 and 360 min after embolization in the TACE-120 and TACE-360 groups, respectively. Of the three groups, AUC(0-30), AUC(30-120), and AUC(120-420) were significantly highest in the transarterial cisplatin infusion group (p < 0.001), the TACE-120 group (p < 0.001), and the TACE-360 group (p < 0.001), respectively. The liver-damaged volume ratio in the TACE-360 group was small (8.20 %) but significantly higher than that in the TACE-120 group (2.67%, p = 0.014). Cisplatin-conjugated soluble gelatin sponge functions as a cisplatin carrier and is associated with tolerable liver damage.

Cisplatin and 5‐fluorouracil in inoperable, stage IV squamous cell carcinoma of the penis

What's known on the subject? and What does the study add? Metastatic or locally advanced squamous cell carcinoma of the penis (SCCP) is generally incurable, but it can be palliated with systemic chemotherapy. Two retrospective studies, involving <10 patients each, showed that cisplatin plus continuous infusion of 5-fluorouracil (5-FU) may be effective and well tolerated. Cisplatin, methotrexate and bleomycin, cisplatin and irinotecan and taxanes can also play an important role for patients with locally advanced/metastatic SCCP. Finally, anti-EGFR therapy may also be effective in advanced SCCP. Although cisplatin plus continuous infusion of 5-FU is widely used in clinical practice for palliation of SCCP, toxicity and efficacy data regarding this schedule include a total of 14 patients with SCCP, treated more than two decades ago. In our retrospective study, cisplatin plus continuous infusion of 5-FU was used for palliative purposes in a homogenous sample of 25 patients with SCCP. Partial responses and stable disease were observed in 8 (32%) and 10 (40%) patients, respectively, with a median progression-free survival of 20 weeks. Neutropenia was the most important grade 3-4 side effect observed, occurring in 20% of patients. These data provide confirmation that such a combination regimen is moderately effective and well tolerated in patients with SCCP. • To investigate the activity and toxicity of 5-fluorouracil (5-FU) as a first-line treatment in metastatic squamous cell carcinoma of the penis (SCCP). • The medical records of 78 patients with SCCP treated between January 2000 and June 2011 at the four participating centres were reviewed. • Data regarding patients treated with first-line 5-FU were extracted. • Patients were included in the study if radiological reports were available for determination of response and progression-free survival (PFS) according to response evaluation criteria in solid tumours (RECIST) 1.1. • Between January 2000 and June 2011, 25 patients were treated with i.v. cisplatin on day 1 followed by 5-FU as a continuous 24-h infusion for 4 days every 3 weeks until disease progression or unacceptable toxicity. Partial responses and stable disease were observed in eight (32%) and 10 (40%) patients, respectively, with a disease control rate of 72%. • Severe neutropenia was the most important grade 3-4 side effect observed, occurring in 20% of patients. • The median (interquartile range [IQR]) PFS was 20 (11-20) weeks and the median (IQR) overall survival (OS) was 8 (7-12) months. • 5-FU is associated with a moderate response rate and is well tolerated in patients with metastatic SCCP.

1573P - The Dopamine D2/D3 Receptor Antagonist APD421 in Combination with Ondansetron Effectively Prevents Acute Cisplatin-Induced Nausea and Vomiting (CINV)

ABSTRACT Conventional dopamine D2 antagonists are among the oldest antiemetics and are considered to be of only moderate efficacy in CINV. Central dopamine D3 receptors have recently been demonstrated to be involved in the emetic reflex arc, but so far no clinical data have been published for any agents acting at these receptors. In preliminary testing, APD421, a potent D2 and D3-antagonist, showed some single-agent efficacy in preventing vomiting and especially nausea caused by cisplatin. We therefore investigated its efficacy in combination with ondansetron at preventing acute-phase CINV. Methods Chemotherapy-naive patients receiving cisplatin ≥ 50 mg/m2 were given single IV doses of APD421 (20 mg) and ondansetron (8 or 16 mg) 30 minutes prior to the cisplatin. Complete response (CR) was defined as no emetic episodes and no rescue medication in the first 24 h after cisplatin infusion. Prospective nausea scores were measured on a 100 mm visual analogue scale at times 2, 4, 8 and 24 h. After the initial 24 h patients received standard antiemetics. Results 17 subjects (15M:2F) have taken part so far, receiving a mean cisplatin dose of 71 mg/m2 (range 64-82 mg/m2), of whom 15 have had CR (88%; 95% CI 72-100%). The mean nausea score is 0.7/100 (range 0-8). 57/66 nausea scores collected have been zero. There have been no clinically-significant APD421-related adverse events. Recruitment will continue until the desired sample size of 23 subjects is reached (expected to be completed July 2012). Final results will be presented. Conclusions The acute-phase efficacy of APD421 in combination with ondansetron in CINV compares favourably with historical data on other 5-HT3-based combinations. Randomised trials in acute and delayed phase CINV are merited. Disclosure G. Fox: The author is an employee and stock-holder of Acacia Pharma. All other authors have declared no conflicts of interest.

671P - A Phase II Trial of Definitive Chemoradiotherapy with S-1 and Cisplatin for Locally advanced Oesophageal Cancer

ABSTRACT Objectives S-1 is an orally active fluoropyrimidine with low gastrointestinal toxicity, capable of enhancing the efficacy of radiotherapy. We report a phase II study of chemoradiotherapy (CRT) combined with S-1 plus cisplatin for locally advanced esophageal cancer (LAEC). Methods CRT comprised two courses: 30-Gy radiotherapy over 3 weeks, plus daily oral S-1 (80 mg/m2/day) for 2 weeks, and a 24-h cisplatin infusion (70 mg/m2) on Day 8. A second identical course was administered after a 2-week break. If patients could not swallow the oral S-1 capsule, it was administered in powder form. In patients who showed an objective response to CRT, at least 2 courses of chemotherapy with S-1 and cisplatin were administered. Results Eighty-three patients participated, 12 with Stage II and 71 with Stage III LAEC. Seventy-seven patients (92.7%) completed CRT. The most frequent adverse events were Grades 3 and 4 neutropenia (38.6%); thrombocytopenia (13.3%), and anemia (9.6%). One patient died on Day 20 from febrile bone marrow aplasia. Non-hematological adverse events were mild. The most common were Grade 2 nausea (32.5%); esophageal pain and oral mucositis (16.9% each); and renal dysfunction (10.8%). Adverse events from the first course of CRT resolved during the 2 weeks interval. Complete response rates in patients with Stage II and Stage III LAEC were 91.7% and 67.6%, respectively. No relapse occurred in patients with Stage II disease, and relapses occurred in 21 (43.8%) of 48 patients with Stage III disease who achieved CR. Median PFS for patients with Stage II and III patients was 6.6 and 1.6 years, respectively. Median survival time was 7 years for Stage II and 2.6 years for Stage III LAEC. Conclusions CRT combined with S-1 plus cisplatin showed promising safety and efficacy, as well as potential to become a standard treatment for LAEC. Disclosure All authors have declared no conflicts of interest.

Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for squamous cell carcinoma of the nasal vestibule: a report of two cases

Squamous cell carcinoma of the nasal vestibule (SCC-NV) is rare among head and neck malignancies. It behaves differently from cancers arising in the nasal cavity and paranasal sinuses, and skin cancer of the external nose. Prognosis is more favorable than nasal cavity tumors and less favorable than skin cancers. We experienced two cases of SCC-NV who were treated with rapid superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT). A 56-year-old male and a 68-year-old female with SCC-NV, classified as T4aN0M0 according to UICC and T2 according to Wang classification, were given superselective intra-arterial infusions of cisplatin, with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity, together with conventional radiotherapy. In both cases, the internal maxillary artery and the facial artery were considered to be feeders of the tumor. No serious adverse events have been observed in either patient to date during follow-up of 7.3 and 5.3 years, respectively. Both patients are alive without disease and show excellent cosmetic results. RADPLAT is considered to be useful for the treatment of patients with SCC of the nasal vestibule.

Randomized Prospective Phase II Study to Compare the Combination Chemotherapy Regimen Epirubicin, Cisplatin, and 5-Fluorouracil With Epirubicin, Cisplatin, and Capecitabine in Patients With Advanced or Metastatic Gastric Cancer

The aim of this study was to compare the efficacy and safety of the epirubicin, cisplatin, and continuous infusion of 5-fluorouracil (ECF) regimen with that of the epirubicin, cisplatin, and capecitabine (ECX) regimen in patients with advanced or metastatic gastric cancer. Patients were randomized to receive either the ECF or ECX regimen. The primary end point was the response rate. The secondary end points were time to progression (TTP), overall survival (OS), and safety. Eighty-five patients were enrolled in the study from January 2003 to March 2007. Forty-five patients received the ECF regimen and 40 patients received the ECX regimen. The objective response rate was 31% [9% complete response (CR) and 22% partial response (PR)] for ECF and 30% (10% CR and 20% PR) for ECX. The disease control rate was 51% and 73%, respectively (P<0.05). Median OS and TTP were 6.8 and 5.5 months, respectively, in the ECF group and 8.3 and 6.0 months, respectively, in the ECX group. The majority of adverse events were grade 1/2. The most frequent grade 3/4 adverse events in both groups were fatigue (ECF 15%, ECX 21%), neutropenia (ECF 16%, ECX 16%), vomiting (ECF 11%, ECX 8%), nausea (ECF 9%, ECX 3%), and anemia (ECF 7%, ECX 5%). The ECX regimen was at least as effective as the ECF regimen with a similar tolerability profile, and could therefore replace the ECF regimen for the first-line treatment of patients with advanced gastric cancer.

Correlation between toxicity and outcome after multimodality therapy of locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus (E) and gastroesophageal junction (GEJ).

e14611 Background: Multiagent concurrent chemoradiation (CRT) and surgery is a standard curative-intent approach for patients (pts) with LRA ACA of the E/GEJ. This single institution retrospective analysis examined whether toxicities occurring during induction chemoradiation (ICRT) were independently prognostic for outcome. Methods: Between 11/99 and 7/06, 152 pts with T3, N1 or M1a ACA of the E/GEJ were entered onto one of two Cleveland Clinic trials. ICRT with 96 hour infusions of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) beginning on day 1 of radiation (30Gy@1.5Gy bid), was followed by surgery and identical post-operative CRT. 75 pts also received 2 years of oral gefitinib. Multivariable Cox analysis was used to identify prognostic factors for overall survival (OS), freedom from recurrence (FFR), locoregional (LRC) and distant metastatic control (DMC). Both clinical features (including demographics, tumor characteristics, symptomatic and pathologic response), and ICRT- related toxicities (including nausea/vomiting, mucositis/dysphagia, neutropenia, thrombocytopenia, neutropenic fever and any unplanned hospitalization) were analyzed. Results: Of the 152 pts enrolled, resection proved possible in 138 (91%). With a median follow-up of 90 (range 57-126) months, the 5-year Kaplan-Meier projected OS is 22%, FFR 24%, DMC 27% and LRC 69%. As expected, in multivariable analysis, earlier clinical stage disease and a pathologic and symptomatic response to ICRT all proved favorable for treatment outcomes. In addition, the development of grade 3-4 (vs. grade 0-2) mucositis and/or dysphagia during ICRT was a significant risk factor for distant recurrence [HR 2.62 (1.34-5.12), p=0.005]; any recurrence [HR 2.08 (1.08-4.00), p=0.027] and death [HR 2.00 (1.07-3.74), p=0.031]. Neutropenic fever was also correlated with distant recurrence [HR 1.82 (1.03-3.22, p=0.039] and any recurrence [HR 2.19 (1.23-3.90) p=0.007]. Conclusions: Neutropenic fever and the development of grade 3-4 mucositis and/or dysphagia during ICRT are independently associated with worse outcomes after multimodality therapy for E/GEJ ACA.

Randomized, single-centered, phase II clinical trial of nimotuzumab plus cisplatin and S-1 as first-line therapy in patients with advanced gastric cancer.

e14668 Background: Nimotuzumab, a humanized IgG1 anti-EGFR monoclonal antibody, has demonstrated efficacy associated with an absence of severe skin toxicity in many phase I/II cancer trials. Methods: This is a single-center, parallel assignment and open-label study randomized to receive a infusion Cisplatin (30mg/m2/d, on day 1 and 2) and oral S-1 (80mg/m2/d, twice daily on day 1-14) every 3 weeks, either alone or together with Nimotuzumab (200 mg as a infusion on day 1, 8 and 15) (CS or NCS) as 1st line in patients with advanced or metastatic gastric cancer. The observation points were ORR, TTP, PFS, 1-year survival rates and safety. Results: 62 patients, 43 men and 19 women, median age 57 years (22-76 years), on good performance status (ECOG PS 0-2, one prior regimen) were treated with NCS (n = 31) or CS (n = 31). Up to 2012-01-16, 57 patients (NCS 30 cases compared with CS 27 cases) have undergone efficacy assessment. The objective response rate (ORR: PR 15) was 50% (15/30) in NCS group compared with (ORR: pCR 2+ PR 15) 63.0% (17/27) in CS group. Disease control rate was 96.7% and 96.3%, respectively. Until the same day, 36 patients have achieved progression in both groups (NCS 15: CS 11), median TTP was 5 months in NCS group compared with 3 months in CS group, and average TTP was 4.9 months and 4 months, respectively. The incidence of adverse events was similar between both groups. Adverse events included grade 3/4 hypo-hemoglobin 13.33%/7.41%, grade 3/4 thrombocytopenia 3.33%/0 and grade 3/4 neutropenia 3.33%/0. One patient experienced grade 3/4 digestive side effects 3.33%/0. Conclusions: The results have demonstrated benefit in TTP improvement. Further investigation is ongoing.

Rapidly alternating chemotherapy and radiotherapy in advanced laryngeal cancers.

e16032 Background: Rapidly alternating chemotherapy and radiotherapy (ACR) is a minor variation of concurrent chemoradiation (CCR). This scheduling and 5-fluorouracil (5-FU) pretreatment followed by cisplatin (FP) treatment have been tested in advanced laryngeal cancers. ACR allows the simultaneous administration of both treatment modalities without increasing toxicity, while pretreatment with 5-FU induces long arrest in S-phase, and enhances cisplatin cytotoxicity (Cancer Chemother Pharmacol, 2008). We conducted a phase II clinical trial to evaluate these hypotheses. Methods: Eligibility: histologically proven squamous cell carcinoma of larynx with stage III or IV, PS 0-1, age &lt;= 75, adequate organ functions, and no prior chemotherapy. Chemotherapy consisted of administration of continuous infusion of 5-FU at 700 mg/m2/day on days 1-5, and 2-hour infusions of cisplatin at 80 mg/m2/day on day 6 (1st week). Once-daily radiotherapy of 36 Gy in 18 fractions was given starting on day 8 (2nd -5th week). Sequentially, FP treatment was repeated twice (6th week) for responders, and radiotherapy of 30 Gy in 15 fractions was given (7-9th week) in total 66 Gy. Results: From 4/2007 to 11/2010, 27 patients (pts) were enrolled. Patient characteristics were median age of 67 (49-74) years; gender, 26 male and 1 female; subsite, glottis 16 pts (59%) and supraglottis 11 (41%); stage, III 15 pts (56%), IV 12 (44%). 23 responders (85%) completed radiotherapy, and of them 20 pts (87%) received two courses of chemotherapy. 20 primary sites (74%) achieved CR by ACR. 4 non-responders (15%) underwent early salvage surgery. 7 pts had salvage surgery and neck dissection. Toxicity was assessed in all pts: 12 grade 3 events (44%; nausea 7, mucositis 4 (15%) and dermatitis 1). There have been no hematological grade 3 or 4 toxicities. The 3-year overall survival and laryngeal preservation rate were 88% and 65%, respectively. Conclusions: In this ACR trial, the rate of mucosal toxicity was equivalent to or less than those with radiotherapy alone, and the laryngeal preservation was equivalent to CCR in spite of 60% glottic carcinomas.

Relationship between treatment duration and outcomes in patients receiving concurrent chemoradiotherapy (CCRT) and surgery for locoregionally advanced (LRA) esophageal and gastroesophageal junction (E/GEJ) adenocarcinoma (ACA).

e14665 Background: Retrospective studies in breast, colon, and head and neck cancer have suggested that delays in administration of adjuvant chemotherapy result in inferior outcomes. We explore this question in patients with LRA E/GEJ ACA. Methods: From 11/99 to 7/06, 152 patients with cT3, N1, or M1a disease were enrolled on one of two clinical trials at the Cleveland Clinic. Two courses of CCRT consisting of 30Gy radiation (@1.5Gy BID) with continuous infusion cisplatin (20mg/m2/day x 4 days) and 5Fu (1000mg/m2/d x 4 days) were given both before and after surgical resection. In the second trial, 75 patients also received gefitinib during the 4 week induction and for a total of two years postoperatively. Using recursive partitioning analysis (RPA), we retrospectively explored the relationship between treatment duration and loco-regional control (LRC), distant metastatic control (DMC), freedom from recurrence (FFR), and overall survival (OS) in the 115 patients (76%) who completed all treatment. Outcomes were estimated using the Kaplan-Meier method and compared among groups using the log-rank test. Results: RPA analysis identified three groups of patients: 19 patients in whom resection occurred ≤45 days from the start of CCRT to resection (short treatment), 63 patients who underwent resection &gt;45 days from the start of CCRT and required &lt;50 days to complete treatment after surgery (intermediate treatment), and 33 patients who underwent resection &gt;45 days from the start of CCRT but required ≥50 days to complete treatment after surgery (prolonged treatment). With a median follow-up of 90 (range 57-126) months, we found that patients with shorter treatment times had better 5 year DMC [64% (short) v 26% (intermediate) v 16% (prolonged); p=0.004], FFR [57% (short) v 23% (intermediate) v 16% (prolonged); p=0.015)], and OS [42% (short) v 30% (intermediate) v 12% (prolonged); p=0.08]. LRC was not different between the groups. Conclusions: Treatment delays in patients receiving multimodality therapy for LRA E/GEJ ACA may result in a greater risk of recurrence and decreased survival.

Prospective study of transarterial infusion of docetaxel and cisplatin to treat non-small-cell lung cancer in patients contraindicated for standard chemotherapy

Our previous retrospective study indicated a good response rate of non-small-cell lung carcinoma (NSCLC) to transarterial infusion chemotherapy, but the precise effect remains unresolved. This prospective study enrolled 25 patients with stage III or IV or recurrent NSCLC without distant metastasis (M1b) who were not candidates for either standard chemotherapy or chemoradiotherapy. The feeding arteries of each tumor detected by angiography were recorded and tumor staining was visually graded on a scale of I–IV. Docetaxel and cisplatin (25 and 25mg/m2, respectively) were administered by arterial infusion. The total dose of each was divided among feeding arteries according to the degree of tumor staining. The end points included response rate, progression-free survival (PFS), overall survival (OS) and toxicity. Correlations between effects and some clinical aspects were investigated. Of 25 patients enrolled between May 2007 and April 2011, 24 of them were evaluable. One complete response and 12 partial responses were achieved for an overall response rate of 52% (95% confidence interval [CI]: 35–69%). The median progression-free survival and overall survival periods were 6.5 (95% CI: 5.4–7.6) and 17.4 (95% CI: 14.2–20.6) months, respectively. The 1- and 2-year survival rates were 81% and 32%, respectively. Grade 3–4 hematological toxicity was not evident. Grade 3 general fatigue or appetite loss developed in patients with performance status (PS) ≥3. Neither grade 4 non-hematological toxicity nor treatment-related death occurred. Among various clinical aspects, ECOG PS significantly correlated with PFS and OS, whereas tumor staining significantly correlated with response. Survival was significantly better for patients with good PS (0 or 1) than poor PS (≥2) and those with, than without grade IV tumor staining. If a sufficient number of feeding arteries are detected and the tumor is appropriately stained, then arterial infusion chemotherapy has favorable response rates with less toxicity for patients with stage III or IV or recurrent NSCLC without distant metastasis (M1b) who cannot tolerate standard chemotherapy.

Transient elevation of serum cystatin C concentrations during perioperative cisplatin-based chemotherapy in esophageal cancer patients

In the present study, the time-concentration profile of platinum (Pt) in plasma was compared to that of serum cystatin C (Cys C) in Japanese esophageal cancer patients receiving perioperative cisplatin-based chemotherapy. Five male and one female patients receiving 2 successive cycles of cisplatin-based chemotherapy combined with 5-fluorouracil, the treatment for esophageal squamous cell carcinoma, participated in this study. The pharmacokinetic parameters in each patient were calculated from the individual plasma Pt concentration-time curve after intravenous infusion of cisplatin using the one-compartment model. Within a week of starting the first cycle of chemotherapy, serum Cys C concentrations increased in all patients from 122.6 to 143.0%, subsequently returning to baseline levels in approximately 10 days. A similar increase in serum Cys C levels also occurred during the second treatment cycle. However, no increase in serum creatinine levels was observed during either treatment cycle. In addition, the concentration of plasma Pt 2 days after treatment in the first and second cycles did not correlate with those of either serum Cys C or creatinine. Finally, the half-life of Pt in plasma during the first treatment cycle was not significantly different from that in the second cycle. These findings suggest that concentration fluctuations in serum Cys C are unlikely to correlate with Pt elimination from the plasma and that renal function estimates based on serum Cys C concentration might be underestimated during perioperative cisplatin-based chemotherapy for esophageal cancer.

The current situation of Sunitinib in treating non-small cell lung cancer

Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor, which are being used in clinic. It can inhibit more than 80 kinds of receptor’s tyrosine kinase, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors, vascular endothelial growth factor receptors (VEGFR), etc. And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer. Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC), by single agent, continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin), which all showed certain effect. The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose: oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1, 8) and cisplatin (80 mg/m2 day 1), administered in 3-week cycles, 66.7% patients achieved partial responses. And adverse effects were mild to moderate in severity (grades 1 to 2). Therapy was generally well tolerated. In summary, all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation

Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

Electroporation-Mediated Transcatheter Arterial Chemoembolization in the Rabbit VX2 Liver Tumor Model

Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability. The purpose of our study was to demonstrate the potential to use electroporation-mediated transcatheter arterial chemoembolization (E-TACE) approaches to increase liver tumor drug uptake while using magnetic resonance imaging (MRI) for intraprocedural optimization of these procedures. Fourteen VX2 tumors were grown in the left hepatic lobes of 8 rabbits. Two tumors were grown in each of 6 rabbits (1 tumor serving as E-TACE-treated tumor and the other as nonelectroporated control), and solitary larger tumors were grown in 2 rabbits (half of the tumor treated with E-TACE, remaining half serving as control). Each rabbit was selectively catheterized under digital subtraction angiography guidance. Baseline MRI was performed to generate tumor contrast enhancement curves following catheter-directed infusion of gadopentetate dimeglumine to estimate the proper time delay between subsequent bolus infusion of cisplatin and application of electrical pulses (electrodes were used to deliver 8, 100-μs, 1300-V pulses at the selected delay interval postinfusion). Three hours after E-TACE, rabbits were euthanized, and tumors were sectioned for inductively coupled plasma mass spectroscopy measurements of platinum concentration (serving as reference standard of cisplatin uptake levels). Inductively coupled plasma mass spectroscopy results demonstrated significantly increased cisplatin uptake in E-TACE-treated tumor tissues, increases of 6.0 ± 3.3-fold compared with transcatheter infusion alone (P = 0.017). Our findings suggest that our E-TACE approach may significantly increase liver tumor drug uptake after targeted transcatheter infusion. MRI measurements permitted intraprocedural guidance during these catheter-directed E-TACE procedures.

The physical and chemical stability of cisplatin (Teva) in concentrate and diluted in sodium chloride 0.9%

Aim of the studyThe subject of study was the stability of cisplatin in concentrate in glass vials and diluted in polyethylene (PE) bags stored at 15–25°C for up to 30 days.Material and methodsOriginal vials of cisplatin injection (1 mg/ml, Teva) were stored at room temperature and subjected to re-piercing after 1, 2, 3, 7, 14, 21, 28 and 30 days following the initial piercing. Cisplatin infusions at nominal concentrations of 0.1 mg/ml were prepared in 0.9% sodium chloride (1000 ml) in PE bags. Chemical stability was measured by means of a stability-indicating high-performance liquid chromatography (HPLC) assay. Physical stability was assessed by visual inspection in normal light.ResultsThe concentration of cisplatin at each sampling time in the analysed solutions remained within 92.0–100.7% of initial concentration, regardless of the container. No changes in colour or turbidity were observed in any of the vials or prepared solutions.ConclusionsCisplatin, both undiluted in glass containers and diluted with NaCl 0.9% in PE bags, remains stable (< 10% degradation) for at least 30 days at room temperature when protected from light.

Evaluation of Urinary α-Glutathione-S-Transferase (α-GST) as a Marker of Early Cisplatin Induced Kidney Injury

Abstract—Cisplatin is a very effective chemotherapeutic, but the risk of nephrotoxicity frequently hinders the use of its higher dose. This study was designed as a prospective observational cohort study to evaluate the efficacy of urinary renal tubular enzyme α-Glutathione-s-transferase(α-GST) for predicting kidney injury in cisplatin treated cancer patients. Venous blood samples were collected from all the patients, before the administration of cisplatin (baseline), and at 12h, 24h, 48h and 20days after cisplatin infusion and a random urine sample was collected before and at 2h , 6h, 12h, 24h and 48h after cisplatin administration. Serum creatinine was estimated by Jaffe‘s method using commercial reagent kit and α –GST was estimated in all the urine samples by colorimetric kinetic assay using NBD-Cl. There was a 20.5% incidence of acute kidney injury after cisplatin administration based on AKIN criteria. The mean urinary α-Glutathione S Transferase levels at different time intervals show a clear temporal rise, especially from 2hrs after cisplatin administration, till 12hrs and at a slower rate thereafter. The AUC of >0.8 for α-GST in all the timed urine samples after cisplatin administration indicated its good performance in predicting kidney injury. Urinary levels of proximal tubular enzyme, α-GST is found to be useful in predicting early kidney injury induced by cisplatin.

A Case of Early-Stage Ovarian Carcinoid Tumor Metastasized to the Liver

We report a case of ovarian carcinoid tumor that recurred with multiple liver metastases and was successfully treated with chemoembolization. A 76-year-old woman was admitted to our hospital presented with abdominal distension and abnormal uterine bleeding for about 6 months. She presented with hyperestrogenic and androgenic manifestations such as vaginal bleeding with endometrial hyperplasia and hirsutism. Magnetic resonance (MR) imaging revealed a large solid and cystic ovarian tumor of 17 cm at maximum diameter. On the basis of the clinical diagnosis of sex cord stromal tumor containing a mature cystic teratoma, she underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology report revealed that the mass in the left ovary was a carcinoid tumor, insular type, with mature cystic teratoma. Two years after surgical treatment, multiple liver metastases were revealed by abdominal CT. Hepatic arterial infusion of cisplatin was performed for 2 courses, and multiple metastatic nodules have remarkably reduced. No established chemotherapy or radiation therapy treatments are currently available for recurrent or advanced carcinoid tumors. Our paper suggests that chemoembolization with cisplatin may be effective in treatment of patients with multiple liver metastases of ovarian carcinoid tumor.

Improvement in urinary retention due to recurrent anastomotic prostate cancer treated with various therapies by intra-arterial infusion of cisplatin and ifosfamide

Although many treatments have been applied to treat hormone-refractory prostate cancer (HRPC), therapeutic outcome is not altogether satisfactory. In the case of locally recurring HRPC, uncontrolled gross hematuria, dysuria, and scalding are often experienced. We report a patient who improved following intra-arterial infusion of cisplatin (CDDP) and ifosfamide (IFM) to treat urinary retention caused by locally recurring HRPC. After chemotherapy, cancer volume was remarkably reduced and symptoms improved.

The Significance of Preoperative Chemotherapy in Evaluation of Recurrent Soft Tissue Liposarcoma Necrosis

To investigate the effect of preoperative induction chemotherapy on treatment of recurrent liposarcoma. 21 patients with recurrent liposarcoma received the treatment of preoperative intra-arterial chemotherapy and surgical resection. Intra-arterial chemotherapy was given by subcutaneous implantable drug delivery system with infusion of cisplatin and doxorubicin followed by caffeine. After treatment, patients were followed up for 39 months. The liposarcoma changes in CT imaging were observed in 18 cases and there were 15 cases with medium or severe pathological changes caused by chemotherapy. At the end of the postoperative follow-up of 39 months, liposarcoma reoccurred locally in 2 cases; pulmonary metastasis occurred in 1 case and death in 3 cases. Preoperative intra-arterial chemotherapy is effective for highly malignant tumors such as recurrent liposarcoma and the judgment of prognosis is based on the postoperative pathological changes of such tumor.