Cisplatin Arm Research Articles

Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study

BackgroundThe aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies. Patients and methodsA multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses. ResultsResults (1029 treated; CS=521/CF=508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR)=0.92 (two-sided 95% confidence interval (CI), 0.80–1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand–foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P<0.047). ConclusionCS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.

Cisplatin-associated nephrotoxicity in clinical trials using serum creatinine (SCr) versus calculated glomerular filtration rate (GFR) as inclusion criterion: A meta-analysis.

272 Background: Treatment with cisplatin (CIS) is associated with increased risk of nephrotoxicity and SCr is commonly used to screen patients for renal dysfunction prior to enrollment in trials using CIS. However, GFR is known to better estimate renal function than SCr. The objective of this trial-level meta-analysis was to indirectly compare incidence of WHO grade ≥3 nephrotoxicity associated with CIS therapy when renal function was assessed using SCr vs. calculated GFR during screening for these trials. Methods: A PubMed literature search was used to identify randomized trials comparing treatment regimens including CIS to those without CIS. Studies were included if they were performed between 1990 and 2005, reported SCr or GFR as inclusion criteria, and reported WHO grade ≥3 nephrotoxic events for both the CIS and non-CIS treatment arms. Studies were excluded if they were review articles, observational, phase 1, non-randomized, did not have a comparator group, or were not reported in English. Inverse variance weighted fixed effects (FE) and random effects (RE) methods were used to estimate the relative risk (RR) associated with CIS vs. non-CIS containing regimens with sub-group analyses of studies using SCr, GFR, and either SCr or GFR for screening. Results: The literature search identified 2359 studies. After exclusion criteria, 549 were reviewed and 24 studies (N=5524 patients) met all inclusion criteria for analysis. Of these, 16 studies used SCr (N=3955), 3 used GFR (N=692), and 5 used SCr or GFR (N=877) for screening. Overall incidence proportion of nephrotoxicity was higher for CIS vs. non-CIS regimens (2.1% vs. 0.7%). Overall RR for CIS vs. non-CIS regimens was 2.49 (95%CI 1.37-4.51, p=0.003). In sub-group analyses, the RR was 2.63 (95%CI 1.29-5.39, p=0.008) for SCr compared to 2.39 (95%CI 0.53-10.64, p=0.26) for GFR and 2.03 (95%CI 0.46-9.02, p=0.35) for either SCr or GFR. The RRs did not differ between the FE and RE methods. Conclusions: This indirect comparison meta-analysis shows CIS is associated with a higher likelihood of nephrotoxicity vs. non-CIS regimens, and may be higher when SCr is used instead of GFR as eligibility criteria.

Molecular Targeted Therapies in the Management of Head and Neck Squamous Cell Carcinoma: Recent Developments and Perspectives

Current development of molecular targeted therapies in oncology is particularly active. This paper is a review of the recent advances in the field of molecular targeted therapies for head and neck squamous cell carcinoma (HNSCC). We analyze not only the recently published and ongoing clinical trials, but also the relevant preclinical studies, in order to identify the future directions of research in the field of HNSCC. As epidermal growth factor receptor (EGFR) signaling pathway plays a key role in the growth of HNSCC, EGFR, with its downstream effectors, represents the main target of the new therapeutic agents currently in development. Today, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted therapy approved for the treatment of HNSCC in patients with locally advanced tumors, in association with radiotherapy, and in patients with recurrent or metastatic disease, in association with platinum-based chemotherapy. Future advances are expected with the integration of cetuximab and other anti-EGFR agents into induction chemotherapeutic regimens or in association with concurrent chemoradiotherapy for locally advanced tumors. Besides EGFR inhibition, new molecular targeted therapies such as mTOR, Src kinase, or IGF-1R inhibitors, acting on other activated molecular signaling pathways, are being developed. As these innovative molecules are beginning to be used in clinical practice, the identification of predictive markers for efficacy and toxicity is now a crucial issue.

Molecular Targeted Therapies in the Management of Head and Neck Squamous Cell Carcinoma: Recent Developments and Perspectives

Current development of molecular targeted therapies in oncology is particularly active. This paper is a review of the recent advances in the field of molecular targeted therapies for head and neck squamous cell carcinoma (HNSCC). We analyze not only the recently published and ongoing clinical trials, but also the relevant preclinical studies, in order to identify the future directions of research in the field of HNSCC. Keywords: Cetuximab, EGFR, Head and neck squamous cell carcinoma, Molecular targeted therapies, Angiogenesis, oropharyngeal tumors, carboplatin, taxane, cisplatin arm.

Radical treatment of locally advanced head and neck cancer with concurrent chemo radiation-cisplatin versus carboplatin: A randomized comparative phase III trial

Context: Concurrent chemoradiation with cisplatin is a standard approach for definitive management of locally advanced head and neck squamous cell carcinoma (LAHNSCC). Carboplatin, though a platinum group of drug, is generally well-tolerated compared to cisplatin. Aim: The aim is whether carboplatin can be a substitute of cisplatin with equivalent response and with less toxicity profile. Settings and Design: Single institutional prospective randomized phase III study. Materials and Methods: Between January 2011 and August 2012, 100 patients LAHNSCC with normal comorbidities were included. The patients in Arm A received injection carboplatin (AUC 6) 3 weeks along with external beam radiotherapy (EBRT) dose 66-70 Gy in conventional fractionation and Arm B received injection cisplatin (100 mg/m 2 ) 3 weeks with same EBRT schedule. Detailed clinical examination along with biopsy for residual or recurrent disease, CT scan of head and neck were done to assess the response, toxicities, and disease-free survival (DFS) in follow-up. Statistical Analysis Used: SPSS version 17 used for statistical calculation. For categorical variables, Chi-Square and Fisher Exact tests were used. For continuous variables, independent samples t test were used with 95% CI. Kaplan-Meier survival analysis was used for comparing the DFS. Results: Overall response rate (CR + PR) were 76.9% in Arm A and 63.6% in Arm B (P = 0.06, non-significant). Statistically significant acute skin (P = 0.003), mucosa (P = 0.003), and upper GI (P = <0.0001) toxicities were found more in cisplatin arm compared to carboplatin arm except acute haematological toxicities. Conclusions: It can be concluded that carboplatin is non-inferior in response with statistically significant less toxicities when compared with cisplatin.

695P - Quality of Life in Flags Trial a Randomized, Comparative, Open Label, Multicenter, Phase 3 of S-1 + Cisplatin (CS) Compared to 5-Fu + Cisplatin (CF) in Untreated advanced Gastric Cancer (AGC) Patients

ABSTRACT Background FLAGS' primary objective was overall survival. We report below the Patient-Reported Outcomes (PRO) (i.e., Quality-of-Life [QoL]) which was one of the secondary objectives. Methods All patients who completed at least one PRO assessment were eligible for analysis. The primary PRO endpoint was the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy – Gastric (FACT-Ga). Patients completed the FACT-Ga at the beginning of Cycles 1, 2, 3, 4, 6 and then every 3 cycles prior to treatment administration. All individual subscales in the FACT-Ga were also evaluated as secondary endpoints. The Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) was administered at the beginning of the first 4 cycles. Results Of the 508 patients dosed at cycle 1 in the CF arm, and the 521 in the CS arm, 456 and 498 respectively completed at least one question on the FACT-Ga and 445 and 486 respectively completed at least 37 items. Compliance to questionnaire fulfillment was more than 80% through Cycle 9. Although there were no overall difference in FACT-Ga scores between the treatment arms and minimal changes over time, an advantage for CS relative to CF was observed for Physical Well-Being (PWB) (51.7% versus 45.1%, p = 0.044). CS treated patients experienced significantly longer time to worsening in PWB scores, with a median time of 4.5 months (95% CI: 3.0 – 5.1) compared to 3.0 months (2.8 – 4.6) with CF (p = 0.014).Patients receiving CS reported higher best and worst score of PWB, Chemotherapy Convenience and Chemotherapy Concerns scores. Conclusions Even if there is little evidence to indicate any difference in FACT-Ga scores, some advantage to CS relative to CF was observed for PWB, one of the secondary PRO endpoints. This advantage was generally consistent across analysis method: time to worsening, best post-baseline score, and worst post-baseline score. CS treated patients did report significantly better Chemotherapy Convenience and Concerns scores, the difference was approximately one-half of a standard deviation generally considered to be a meaningful difference. Disclosure All authors have declared no conflicts of interest.

Gemcitabine versus cisplatin concurrent with radiation therapy in locally advanced head and neck squamous cell carcinoma.

5557 Background: In locally advanced head and neck squamous cell carcinoma (HNSCC) weekly cisplatin concurrent with radiation therapy is the standared treatment. However some patients cannot tolerate cisplatin. So we conduct a prospective randomized trial comparing cisplatin versus gemcitabine. Methods: This trial was done in Kasr El-Ainy Center of Clinical Oncology and Radiation therapy (NEMROCK), during the period from March 2010 till June 2011. Sixty patients with locally advanced HNSCC were randomized to receive Cisplatin (30 mg/m2) weekly for 6 consecutive weeks (30 patients) or Gemcitabine (50 mg/m2) weekly for 6 consecutive weeks (30 patients) both concomitant with radiation therapy reaching a dose of 70 Gy over 7 weeks. Primary end points include response rate, progression free survival and toxicity. Toxicities were graded according to NCI-CTCAE v3.0. Results: Thewhole study group included 48 (80%) males and 12 (20%) females. Mean age was 47.9 (± 6.5) years (range 26-61). Both arms were comparable regarding their age, gender, performance status and stage. There were 9 (30%) CR, 7 (23.3%) PR, 2 (6.7%) SD and 12 (40%) PD in cisplatin arm versus 12 (40%) CR, 4 (13.3%) PR, 1 (3.3%) SD and 11 (36.7%) PD in gemcitabine arm. Median progression free survival (PFS) in cisplatin arm was 9 months versus 11months in gemcitabine arm with a hazard ratio of 0.08 (95% CI 0.005 – 1.47). We did not reach median overall survival. Radiotherapy induced skin toxicity (slight or patchy atrophy), nausea, vomiting, mucositis, salivary gland affection and weight loss were equally distributed in both arms. Dysphagia and fatigue were markedly higher in gemcitabine arm. While infection and neutropenia were slightly higher in cisplatin arm. Conclusions: Weekly gemcitabine 50mg/m2 concomitant with radiotherapy was found to be of equal efficacy and toxicity comparable with weekly cisplatin in the treatment of locally advanced HNSCC.

Predictive impact of RRM1 protein expression on vinorelbine efficacy in NSCLC patients randomized in a chemotherapy phase III trial.

10617 Background: Platinum based doublets remain the cornerstone of treatment in non-small cell lung cancer (NSCLC) and often includes gemcitabine. A biomarker predicting sensitivity to this antimetabolite would represent a major step forward in the management of advanced disease. Ribonucleotide reductase subunit M1 (RRM1) has been of some value in NSCLC but evidence is not uniform. Accordingly, we explored the predictive role of RRM1 in patients with advanced NSCLC. Methods: 443 patients with advanced NSCLC were randomized in a phase III trial to regimen A (paclitaxel and cisplatin with gemcitabine) or regimen B (cisplatin and vinorelbine). Immunohistochemical evaluation of RRM1 was performed on mainly bioptic material and correlated to response rates, progression free survival (PFS) and overall survival (OS). Results: 261 (58.9%) patients had representative tissue samples for RRM1 evaluation. Disease control rate, PFS and OS were significantly improved in patients with RRM-negative tumors receiving regimen B as compared to patients with RRM-positive tumors (68.8% vs. 31.2%, P = 0.046 , 6.90 months (mths) (95% CI 5.83-7.96) vs. 3.93 mths (95% CI 3.11-4.76), P = 0.000 and 11.57 mths (95% CI 9.65-13.48) vs. 7.4 mths (95% CI 5.37-9.43), P = 0.002, respectively). However, this was not the case for patients receiving regimen A (67.6% vs. 32.4%, P = 0.366, 6.73 mths vs. 7.6 mths, P = 0.207, 11.07 mths vs. 12.37 mths, P = 0.103, respectively ). Together with histological subtype, RRM1-positivity emerged as the only other significant prognostic variable with a hazard ratio of 1.56 (95% CI 1.38-2.35, P = 0.033) in multivariate analysis for patients treated with regimen B. Conclusions: RRM1 protein expression was without predictive impact in patients treated with cisplatin, paclitaxel and gemcitabine. Surprisingly, the predictive power proved robust in the cisplatin and vinorelbine arm across classic endpoints confirmed by multivariate analysis. These findings may suggest that RRM1 is involved in vinorelbine sensitivity and warrant further research which will be presented shortly.

Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies

S-1 is a combination of three pharmacological compounds, namely tegafur, gimeracil, and oteracil potassium. Tegafur is a prodrug of 5-fluorouracil (5-FU), an oral fluoropyrimidine, and it has been developed as a replacement for infusional 5-FU therapy. S-1-based chemotherapy and the combination of S-1 and cisplatin are the most reasonable first-line standards for unresectable advanced gastric cancer in Japan. However, the application of S-1 for gastric cancer has been delayed in Western countries. One reason for this delay is that the pharmacokinetics of tegafur is affected by polymorphisms in cytochrome P-450 2A6, and consequently 5-FU concentrations in the plasma are more likely to be elevated in patients from Western countries. Although the dose of S-1 was reduced compared with the approved dose in Japan, a global Phase III study reported similar results regarding overall survival between S-1 plus cisplatin and infusional 5-FU plus cisplatin arms. Significant safety advantages were observed in the S-1 plus cisplatin arm compared with the infusional 5-FU plus cisplatin arm. S-1 plus cisplatin has become acceptable for Western countries, also, as a choice for unresectable advanced gastric cancer. Comparisons with capecitabine and combination of several targeting agents with S-1 are expected in the future.

Docetaxel- and 5-FU-concurrent radiotherapy in patients presenting unresectable locally advanced pancreatic cancer: a FNCLCC-ACCORD/0201 randomized phase II trial's pre-planned analysis and case report of a 5.5-year disease-free survival

BackgroundTo explore possible improvement in the treatment of locally advanced pancreatic carcinoma (LAPC) we performed a randomized, non-comparative phase II study evaluating docetaxel - plus either daily continuous 5 FU or weekly cisplatin concurrent to radiotherapy. We report here the results of the docetaxel plus 5 FU regimen stopped according to the interim analysis. The docetaxel plus cisplatin arm was continued.MethodsForty (40) chemotherapy-naive patients with unresectable LAPC were randomly assigned (1:1) to either continuous fluorouracil (5-FU) 200 mg/m2/day (protracted IV) and docetaxel (DCT) 20 mg/m2/week or DCT 20 mg/m2 and cisplatin (CDDP) 20 mg/m2, plus concurrent radiotherapy for a period of 6 weeks. The radiation dose to the primary tumor was 54 Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate (NPR). Secondary endpoints were tolerance, objective response rate, and overall survival. Accrual was to be stopped if at 6 months more than 13 disease progressions were observed in 20 patients.ResultsEighteen (18) progressions occurred at 6 months in the 5-FU-DCT arm. Six-month NPR was 10% (95%CI: 0-23). Six and 12-month survivals were 85% (95%CI: 64-95) and 40% (95%CI: 22-61); median overall survival was 10.1 months. Median progression-free survival was 4.3 months. We report the case of one patient who was amenable to surgery and has been in complete response (CR) for 5.5 years. Toxicities grade ≥ 3 were reported in 75% of patients; no treatment-related death occurred. Severe toxicities were mainly vomiting (35%), abdominal pain (10%) and fatigue (10%).ConclusionsCombination of 5-FU, docetaxel and radiotherapy has inadequate efficacy in the treatment of LAPC despite good tolerance for the 5-FU-DCT regimen.Trial RegistrationClinicalTrials.gov: NCT00112697

Phase II Evaluation of Phenoxodiol in Combination With Cisplatin or Paclitaxel in Women With Platinum/Taxane-Refractory/Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

Chemoresistance is a major limitation in the treatment of ovarian cancer. Phenoxodiol is a novel biomodulator capable of reversing chemoresistance in vitro and in vivo. In this study, we determined the safety and efficacy of intravenous phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant ovarian cancers. Thirty-two patients were randomized to 1 of 2 treatment arms according to their previous responses: (1) platinum refractory/resistant, cisplatin (40 mg/m intravenous) weekly on day 2 + phenoxodiol (3 mg/kg) weekly on days 1 and 2 and (2) taxane refractory/resistant, paclitaxel (80 mg/m IV) weekly on day 2 and phenoxodiol (3 mg/kg) weekly on days 1 and 2. Patients continued on treatment until complete response, disease progression, unacceptable toxicity, or voluntary withdrawal. There were no treatment-related deaths. There was only one treatment-related hospitalization and 2 grade 4 toxicities. In the cisplatin arm, there were 3 partial responses, 9 patients (56%) achieved stable disease, 4 (25%) progressed, and the overall best response rate was 19%. In the paclitaxel arm, there was one complete response and 2 partial responses, 8 patients (53%) achieved stable disease, 4 patients (27%) progressed, and the overall best response rate was 20%. The combination of IV phenoxodiol with cisplatin or paclitaxel was well tolerated in this study. Cisplatin-phenoxodiol was particularly active and warrants further study in patients with platinum-resistant ovarian cancer.

Abstract PD01-01: Cetuximab + Cisplatin in Estrogen Receptor-Negative, Progesterone Receptor-Negative, HER2-Negative (Triple-Negative) Metastatic Breast Cancer: Results of the Randomized Phase II BALI-1 Trial

Abstract Background: The epidermal growth factor receptor (EGFR) plays a role in triple-negative (estrogen receptor-, progesterone receptor-, HER2-negative) breast cancer (TNBC). This randomized, phase II study investigated the combination of the EGFR monoclonal antibody cetuximab and cisplatin in the treatment of metastatic (m) TNBC. Methods: Patients (pts) with mTNBC who had received ≥1 prior chemotherapy regimen for metastatic disease, were randomized 2:1 to treatment with either: cetuximab (400 mg/m2 initial dose then 250 mg/m2 weekly) + ≥6x 3-weekly cycles of cisplatin (75 mg/m2, d1); or ≥6x 3-weekly cycles of cisplatin alone. In the cisplatin arm, pts with disease progression (PD) during the 6 cisplatin cycles could switch to cetuximab plus cisplatin and those with PD after the 6 cycles could receive cetuximab alone. The primary endpoint was best overall response. Simultaneous null hypotheses assumed that the overall response rate (ORR) in the combination arm was ≥20% and that the ORRs were equal in both arms. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. All statistical tests were performed at alpha-level 0.1 Results: 173 pts were included in the intention-to-treat population: 115 were randomized to cetuximab/cisplatin and 58 to cisplatin. The cetuximab/cisplatin and cisplatin arms were well balanced for patient and disease characteristics (randomization strata, 73% first and 27% second line in both arms). Differences included: age ≥65 years (19.1% vs 12.1%) and lung metastases (55.7% vs 44.8%). 30 pts receiving cisplatin alone switched to cetuximab/cisplatin after first PD. 79.6% of patients on cetuximab/cisplatin and 73.7% on cisplatin received ≥90% of the relative dose intensity of cisplatin. Adverse events (AEs) were manageable and in line with what was expected from the different agents (grade 3/4 AEs are shown in the Table). Grade 3/4 AEs (%) Adding cetuximab to cisplatin nearly doubled the ORR: 20.0% (95% CI 13.1%, 28.5%) vs 10.3% (95% CI 3.9%, 21.2%) (p=0.5 for testing ORR against 20.0%), with an odds ratio of 2.126 (90% CI 0.945, 4.786, p=0.11). Cetuximab/cisplatin was associated with a significant 32.5% reduction in the risk of disease progression compared with cisplatin alone HR 0.675 (95% CI 0.470, 0.969, p=0.032). Median PFS times were 3.7 and 1.5 months, respectively. The benefits of cetuximab/cisplatin over cisplatin on ORR and PFS were observed consistently across sub-groups (according to patient, disease and treatment characteristics), but sample sizes were small. OS results will be presented at the meeting. Conclusions: Adding cetuximab to cisplatin increased the ORR compared with cisplatin alone and significantly improved PFS in mTNBC. Safety was manageable. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD01-01.

Comparison of vinorelbine with cisplatin in concomitant chemoradiotherapy in head and neck carcinoma

Aim:Head and neck cancer is one of the most commonly occurring malignancies in the world. In India, the most commonly occurring head and neck cancers are those of the oral cavity and the pharynx. The majority of these cancers present with stage III/IV disease. Surgery and radiation therapy are the main treatment modalities. Concomitant chemoradiation is being investigated with the goal of improved local control that translates into improved survival. In this background, we have started this prospective randomized trial to ascertain the dose, schedule and sequence of therapy and to note whether Vinorelbine as radiosensitizer is equally effective as Cisplatin, comparing compliance, local control and toxicity.Patients and Methods:Forty patients of advanced head and neck cancer were randomized into two arms. Arm A received weekly injection Cisplatin 40mg/m2 along with radiation. Arm B received weekly injection of Vinorelbine 6mg/m2 along with radiation. Radiotherapy was delivered at a dose of 6,600-7,000 Gy in conventional fractionation in a telecobalt machine.Results:The complete response (CR) rate was higher in arm B (90%) than in arm A (70%). Major toxicities included neutropenia, anemia, mucositis and nausea.Conclusion:Concomitant chemoradiation with Vinorelbine produced more CR than chemoradiation with Cisplatin in advanced head and neck cancer. Toxicities were more in the Cisplatin arm, but they were manageable. Although a majority of the study was performed using Cisplatin as the radiosensitizer, Vinorelbine can be recommended as radiosensitizer in advanced head and neck malignancy.

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

Weekly cisplatin or gemcitabine concomitant with radiation in the management of locally advanced carcinoma cervix: results from an observational study.

The use of non-platinum drugs in concurrent chemoradiation in carcinoma cervix has not been well explored and hence a two arm study was planned to compare the outcome of concomitant cisplatin or gemcitabine in locally advanced carcinoma cervix. Thirty six patients were evaluated in this study for response rates and complications. These patients were divided into two arms, sixteen patients in the cisplatin arm and twenty patients in the gemcitabine arm. Cisplatin and gemcitabine were given as i.v. infusion at doses of 40 mg/m(2) and 150 mg/m(2) respectively for five weeks concomitant with radiotherapy. All patients had received pelvic radiotherapy to a dose of 50 Gy/25 fraction/5 weeks by four field box technique followed by high-dose-rate brachytherapy (3 sessions, each of 7.5 Gy to point A). Median follow up was of 10.4 months (range, 3 to 36 months) and 10.9 months (range, 2 to 49 months) in the cisplatin and gemcitabine arms, respectively. At first follow up, 68.8% in the cisplatin arm and 70% in the gemcitabine arm had achieved complete response (p=0.93). Similar response rates were noted in different stages in both arms. None of the patients except one developed grade 4 toxicity. Similar toxicity profiles were observed in both arms. Local disease control, distant disease free survival and overall survival was 68.8% vs. 70%, 93.8% vs. 85%, 68.8% vs. 60% in the cisplatin and gemcitabine arms, respectively. Weekly gemcitabine had similar disease control and tolerable toxicity profile with cisplatin. Gemcitabine may be used as an alternative to cisplatin in patients with compromised renal function.

Randomized, Multicenter, Phase III Trial of Heptaplatin 1-hour Infusion and 5-Fluorouracil Combination Chemotherapy Comparing with Cisplatin and 5-Fluorouracil Combination Chemotherapy in Patients with Advanced Gastric Cancer

Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer. One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m(2)) or cisplatin (60 mg/m(2)) was given over 1 hour with 5-FU (1 gm/m(2)) on days 1~5 every 4 weeks. At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths. Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.

Phase II Trial of Paclitaxel and Cisplatin in Patients with Extensive Stage Small Cell Lung Cancer: Cancer and Leukemia Group B Trial 9430

Cancer and Leukemia Group B trial 9430 was a randomized phase II trial which investigated the safety and activity of four novel doublets in untreated extensive stage small cell lung cancer. The results of the paclitaxel and cisplatin arm have not been reported. Patients received paclitaxel 230 mg/m followed by cisplatin 75 mg/m on day 1 every 21 days. All patients received granulocyte colony stimulating factor 5 microg/kg/d beginning on day 3 of each cycle. The patient characteristics of the 34 patients assigned to this treatment arm were: median age 61.5 years (range 41-82), male (76%), performance status 0 (41%), 1 (32%), and 2 (26%). An objective response was observed in 23 patients (68%; 95% confidence interval (CI): 49-83%); 2 complete responses (6%) and 21 partial responses (62%). Median progression-free survival time was 5.6 months (95% CI: 4.8-7.1 month), and median overall survival time was 7.7 months (95% CI: 7.2-12.6 months). The 1-year survival rate observed was 29% (95% CI: 15-45%). Grade 3/4 neutropenia and thrombocytopenia was observed in 5 (15%) and 4 (12%) patients, respectively. Two patients developed febrile neutropenia including one patient who died of neutropenic sepsis. Grade 3/4 nonhematologic observed were: sensory neuropathy in eight patients (24%); and hyperglycemia, malaise and nausea were all observed in four patients (12%). Cancer and Leukemia Group B will not pursue further investigation of paclitaxel and cisplatin due to the modest activity and the toxicity observed on this trial.

Chemoradiation in locally advanced cervical cancer : A randomized trial

Abstract Background: Radiation with concurrent chemotherapy (weekly cisplatin) is currently standard of care for locally advanced cervical cancer. Gemcitabine, a pyrimidine analogue is a potentially radio-sensitizing drug. We compared cisplatin and gemcitabine in the treatment of locally advanced cervical cancer. Methods: 90 patients with locally advanced squamous cell cancer of the cervix (stage IIB-IVA) were randomized to receive either cisplatin 40mg/m2 weekly or gemcitabine 150 mg/m2 weekly (45 patients in each arm) along with external beam radiation (50Gy in 25# over 5 weeks). This was followed by three insertions of high dose radiation (HDR) intracavitary brachytherapy one week apart. Results: At a median follow up of 13months, 25 (55.56%) patients were in complete response (CR) in the cisplatin arm compared to 22 patients (48.89%) [p=0.67] in gemcitabine arm. 10 patients (22.22%) in cisplatin arm had either died or lost to follow up compared to 11 patients in gemcitabine (24.44%) arm. Nausea/vomiting was higher in cisplatin arm. Diarrhea, skin reaction and hematological toxicity were more in gemcitabine arm. Conclusion: Cisplatin seems to be a better option than gemcitabine when used concurrently with radiation for locally advanced cervical cancer both in terms of response and toxicity.

Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy?

Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy?

Concurrent chemoradiation in locally advanced head and neck cancers: A comparison of weekly paclitaxel with cisplatin-based regimen

17032 Background: Concurrent cisplatin-based chemoradiation is the standard of care for patients with unresectable locally advanced squamous cell carcinoma of head and neck (LA-SCCHN) with 5-year locoregional control rates between 35–70%. Taxane-based chemotherapies might improve locoregional control as has been shown in phase I and II trials. This retrospective analysis compares the outcome and toxicity of weekly paclitaxel with weekly cisplatin-based concurrent chemoradiation in LA-SCCHN. Methods: 107 patients of unresectable stage III, IVA and IVB cancers of oropharynx, hypopharynx and larynx were retrospectively analyzed for outcome and toxicity. A retrospective chart review was used to create a data base of clinical and pathologic characteristics of these patients using Microsoft Excel. 58 patients received concurrent weekly paclitaxel (30 mg/m2) and 49 patients were administered weekly cisplatin (40 mg/m2) during radiation therapy with conventional fractionation and curative intention. Results: The median duration of follow up was 12 months in each group (range 3–53 months). In the paclitaxel arm, 43 (74.13%) patients remained alive and disease-free whereas in the cisplatin arm, 33 (67.34%) patients were alive disease-free. This difference was not statistically significant (p=0.34). In the paclitaxel group, among the patients completing radiation in 47 or less days, 26 (81.25%) were alive and disease free in comparison with 17 (65.38%) in those completing radiation in longer than 47 days (odds ratio = 2.29, p=0.16). In the cisplatin arm, alive disease-free status was seen in 18 (67.34%) patients completing radiation in 47 days or less and 15 (65.21%) in those taking longer than 47 days to complete radiation therapy (odds ratio=1.2, p=0.76). The projected mean locoregional relapse free survival in Paclitaxel arm was 33.42 months, and 32.18 months in the cisplatin arm (p=0.73). The 2-year locoregional relapse free survival was 60% in the Paclitaxel arm and 52% in the Cisplatin arm. Conclusion: At 12 months median follow up, weekly paclitaxel-based concurrent chemoradiation regimen provides no additional efficacy and tolerability benefits over and above those provided by weekly cisplatin. No significant financial relationships to disclose.