Adjuvant Cisplatin Chemotherapy Research Articles

Racial disparities in treatment and outcomes of pediatric hepatoblastoma.

10062 Background: Hepatoblastoma is the most common malignant liver tumor which affects pediatric patients. However, the incidence is rare with 100 cases reported per year.1 Current management consists of surgery and adjuvant cisplatin chemotherapy and radiation depending on tumor histology, resectability, and metastasis.2 However, due to its rarity, optimal treatment protocol remains unclear. The 5-year overall survival rate in the US is approximately 57-69%1. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with hepatoblastoma from 2004 to 2020 using the histology codes 8970 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, and ANOVA tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: This study identified 1215 patients with hepatoblastoma. Black patients had a significantly lower median survival rate compared to White and other race patients (126.2 months vs 165.4 months vs 166.1 months; all p<0.05). Black patients were more likely to be from low-income households than White patients (29.6% vs 17.3%; p<0.05). The mean age of diagnosis was higher for Black patients compared to White patients (2.42 vs 1.99; p<0.05). Black patients were less likely to receive surgery (63.5% vs. 75.4%; p<0.05). Black patients on average had shorter distances to travel from their residence to the hospital (30.61 vs. 59.52 miles; p<0.05). Black patients had longer mean stay times compared to white patients (16.7 days vs 11.2 days; p<0.05). There was no significant difference in survival across incomes. When comparing Black and White patients there was no significant difference in insurance type, surgical margins, grade, stage, size of tumor, regional lymph nodes and time of diagnosis to treatment. No significant difference was shown between adjuvant therapies including chemotherapy and radiation. Conclusions: This study showed Black patients experienced inferior overall survival when diagnosed and treated for hepatoblastoma compared to White patients. This population was less likely to receive surgery, older when diagnosed, and had longer hospital stays. Poorer outcomes suggest a disparity in hepatoblastoma treatment.

Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial.

BackgroundAlthough platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC.MethodsEnrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival (DFS), and overall survival (OS).ResultsA total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity (RDI) was 79% for S-1 and 80% for cisplatin. The 2-year DFS rate was 42.1%, and 2-year OS rate was 83.3%.ConclusionsThis study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy.Trial registrationThis study was registered on the UMIN clinical study registration site (protocol ID: UMIN000016191) on December 1, 2015.

Commentary on “A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy—A single-institution experience.”

BackgroundManagement of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.” ObjectiveTo evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). Materials and methodsWe, retrospectively, reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18–70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. ResultComplete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). ConclusionGC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

O2-2-5 - Survival data of postoperative adjuvant chemotherapy of cisplatin plus vinorelbine for completely resected NSCLC

Although the efficacy of postoperative adjuvant cisplatin (CDDP) based chemotherapy, such as the combination of CDDP and vinorelbine (VNR) has been established for surgically resected non-small-cell lung cancer (NSCLC), there has been a few reports about the survival data of Asian patients treated with the combination of CDDP and VNR as adjuvant chemotherapy. We retrospectively have evaluated patients received adjuvant chemotherapy with the combination of CDDP and VNR, at the Shizuoka Cancer Center between February 2006 and October 2011. One hundred surgically resected NSCLC patients were included in this study. The characteristics of the patients were as follows: median age 63 years (range: 36-74); female 34%; never smokers 20%; non-squamous 73%. Pathological stages IIA/IIB/IIIA were observed in 31/22/47%. The five-year overall survival (OS) rate was 73% and the 2-year OS rate was 93%. The five-year relapse-free survival (RFS) rate was 53% and the 2-year RFS rate was 62%. A univariate analysis of prognostic factors showed that patient characteristics (gender, histology, pathological stage) and dose intensity of cisplatin were not significantly associated with survival. In 48 patients experienced recurrence of NSCLC, five-year survival after recurrence rate was 29%, and median survival after recurrence was 37 months. Our results suggested that the prognosis of surgically resected NSCLC patients, who were treated with the combination of CDDP and VNR as adjuvant chemotherapy, might be better than previous results of adjuvant chemotherapies for NSCLC patients.

A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy—A single-institution experience

BackgroundManagement of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin–preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.” ObjectiveTo evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). Materials and methodsWe retrospectively reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18–70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. ResultComplete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). ConclusionGC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

Survival and Side Effects of Cisplatin/Cyclophosphamide and Carboplatin/Paclitaxel Adjuvant Chemotherapy in Stage IC-IV Ovarian Cancer

Objective: To compare the survival and side effects in epithelial
 ovarian cancer patients receiving adjuvant chemotherapy of cisplatin/
 cyclophosphamide and carboplatin/paclitaxel.
 
 Method: We recruited epithelial ovarian cancer patients receiving
 cisplatin/cyclophosphamide (group A) or carboplatin/paclitaxel
 (group B) adjuvant chemotherapy after surgery. Chemotherapy was
 given for six cycles. Overall survival and side effects were assessed.
 
 Result: A total of 49 patients were recruited, consisting of 25 patients
 for group A and 24 patients for group B. In this study, the overall
 survival of stage IC-IV ovarian cancer patients was 37.3 months in
 group A (95%CI=31.86-43.46) and 35.5 months (95%CI= 13.93-
 43.46) in group B (p

Knockdown of GRP78 enhances cell death by cisplatin and radiotherapy in nasopharyngeal cells.

Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream approaches in the treatment of nasopharyngeal carcinoma (NPC). These have been shown to effectively improve the outcome and reduce tumor recurrence. However, radiotherapy and chemotherapy resistance during the course of treatment has become more common recently, resulting in the failure of NPC therapy. Therefore, new therapeutic strategies or adjuvant drugs are urgently needed. The current study was designed to look for new treatment strategies or auxiliary drugs in the treatment of NPC. Two human NPC cell lines, HNE1 and HNE1/DDP, were used to examine the relationship between endoplasmic reticulum stress and cell resistance to ionizing radiation (IR) and cisplatin (DDP). Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Meanwhile, propidium iodide (PI) staining and PI/Annexin V staining were used to observe cell apoptosis. Finally, western blot was used to detect the endogenous expression of glucose-regulated protein 78 (GRP78) and other apoptosis-related proteins. GRP78 small interference RNA was transfected using Lipofectamine 2000. Compared with HNE1/DDP, IR and DDP increased the cell apoptosis and inhibited the cell proliferation of HNE1. Inhibition of GRP78 can reverse IR and DDP resistance in NPC cells by PI/Annexin V staining. Knockdown of GRP78 upregulates the expression of pro-apoptotic proteins and downregulates the expression of antiapoptotic proteins. These results indicate that HNE1 is more sensitive to DDP and IR than HNE1/DDP. Knockdown GRP78 can reverse IR and DDP resistance in NPC cells. Inhibition of GRP78 gives us a new target to overcome resistance to radiotherapy and chemotherapy of NPC cells. Thus, this study should be further explored in vivo and assessed for possible clinical applications.

Prognostic significance of the concomitant existence of lymphovascular and perineural invasion in locally advanced gastric cancer patients who underwent curative gastrectomy and adjuvant chemotherapy.

In this study, we evaluated the prognostic significance of the concomitant existence of lymphovascular invasion and perineural invasion in patients with advanced gastric cancer. A total of 206 consecutive patients with Stage II or III gastric cancer who underwent curative D2 gastrectomy and adjuvant chemotherapy from April 2004 to December 2011 were analyzed. Patients were classified into four groups according to the presence (+) or absence (-) of lymphovascular invasion and perineural invasion: lymphovascular invasion-/perineural invasion- (n = 33), lymphovascular invasion+/perineural invasion- (n = 31), lymphovascular invasion-/perineural invasion+ (n = 54) and lymphovascular invasion+/perineural invasion+ (n = 88). A total of 136 patients (66.0%) received 5-fluorouracil plus cisplatin adjuvant chemotherapy and 70 patients (34.0%) received TS-1. During the median follow-up period of 35.18 months, the median disease-free survival times for lymphovascular invasion-/perineural invasion-, lymphovascular invasion+/perineural invasion- and lymphovascular invasion-/perineural invasion+ were not reached at the time of analysis; however, median disease-free survival for lymphovascular invasion+/perineural invasion+ was the worst (36.73 months, P = 0.001). The median overall survival in the four groups was also not reached at the time of analysis; however, median overall survival with lymphovascular invasion+/perineural invasion+ was the poorest (P = 0.002). In a multivariate analysis, lymphovascular invasion+/perineural invasion+ was an independent prognostic factor for both disease-free survival (hazard ratio = 1.940, 95% confidence interval 1.157-3.252, P = 0.012) and overall survival (hazard ratio = 2.973, 95% confidence interval 1.561-5.662, P = 0.001). The concomitant existence of lymphovascular and perineural invasion has a significant prognostic impact on disease-free survival and overall survival in patients with Stage II or III gastric cancer.

Impact of an Adjuvant Chemotherapeutic Regimen on the Clinical Outcome in High Risk Patients with Upper Tract Urothelial Carcinoma: A Japanese Multi-Institution Experience

Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy.

Multi-institutional quality care initiative (QCI) to improve the care of patients with invasive bladder cancer (BlCa).

298 Background: Level 1 evidence supports a survival benefit for BlCa pts that receive periop cisplatin chemotherapy in addition to radical cystectomy (RC). Underutilization of multimodal therapy has been reported nationally. We instituted a multicenter QCI to improve the use of periop chemotherapy. Methods: A two phase effort was initiated at 16 academic institutions. Phase 1 was initiated in 2010 and designed to evaluate baseline patterns of periop chemotherapy use for T2-4N0M0 BlCa pts that underwent RC between 2003-2008. Phase 2 was a prospective QCI. The quality indicators included (1) referral to medical oncology for consideration of multimodality therapy, (2) neoadjuvant, if recommended, be cisplatin based and at least 3 cycles, (3) adjuvant, if recommended, be cisplatin based and at least 3 cycles, (4) all treatment be completed within 6 months. Data on all eligible pts were collected prospectively for 12 months on a web-based survey system. Results: All 16 centers participated in phase 1. Of 4,344 pts on whom data was available, 34% received periop chemotherapy. Neoadjuvant and adjuvant therapy use was 14% and 20%, respectively. 65% of pts receiving periop chemotherapy were treated with a cisplatin-based regimen. Of those treated neoadjuvantly, cisplatin was received in 70% of cases. Nine of the 16 institutions completed phase 2 data collection. Over 700 pts that underwent RC were evaluated. 395 pts with T2-4N0M0 disease were deemed eligible for data entry. Fifty-six percent of eligible pts received periop systemic chemotherapy. Of this 56%, 47% received neoadjuvant cisplatin chemotherapy and 9% received adjuvant cisplatin chemotherapy. This represented a 64.7% increase in the use of any periop chemotherapy and a 3.4 fold increase in neoadjuvant chemotherapy compared to baseline data. Conclusions: We have successfully completed a multi-institutional QCI to improve the use of periop chemotherapy in pts undergoing RC for resectable, non-metastatic bladder cancer. Our data demonstrates that significant improvements can be achieved in not only overall use of periop chemotherapy but most notably in the use of neoadjuvant chemotherapy.

Efficacy and Safety of Platinum Combination Chemotherapy Re-Challenge for Relapsed Patients with Non-Small-Cell Lung Cancer after Postoperative Adjuvant Chemotherapy of Cisplatin plus Vinorelbine

Background: There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Methods: Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Results: Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Conclusion: Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC.

Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced apoptosis in human nasopharyngeal carcinoma cells

Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream treatments for nasopharyngeal carcinoma (NPC), which effectively improve the outcome and reduce tumor recurrence. However, the resistance mechanism(s) involved in radiotherapy and chemotherapy, which is the main barrier in NPC treatment, remains undefined. Therefore, there is an urgent requirement for the identification of new therapeutic strategies or adjuvant drugs. In the present study, the effects of autophagy inhibitors on endoplasmic reticulum (ER) stress-induced autophagy was investigated. Combining 3-methyladenine (3-MA) with cisplatin (DDP), ionizing radiation (IR), 2-deoxy-D-glucose (2-DG) or tunicamycin (TM) resulted in enhanced cell death, as revealed by MTT and colony formation assays. Flow cytometry results demonstrated that the sensitivity of NPC cells to DDP- and IR-induced apoptosis was not significant. DDP, IR, 2-DG and TM induced ER stress and autophagy. Using fluorescence microscopy, 3-MA was identified to increase the apoptotic cell death induced by DDP, IR, 2-DG or TM. In addition, 3-MA inhibited the increased autophagy induced by DDP, IR, 2-DG or TM, as demonstrated by western blot analysis and immunocytochemistry results. Results of the present study indicate that autophagy acts as a protective mechanism response to the apoptosis induced by DDP, IR, 2-DG or TM.

Tolerability and toxicity of adjuvant cisplatin and gemcitabine for treating non-small cell lung cancer

Background The combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer (NSCLC). But this doublet has considerable toxicity and unfavorable tolerability, and results in poor compliance. The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC, but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting. Methods From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m2) and gemcitabine (1250 mg/m2) between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records. Results A total of 132 patients met the criteria and were included in the study, 96 were male (72.7%) and 36 were female (27.3%). Median age was 60.5 years old, range 29-75 years, and 41.7% of patients were ≥65 years old. Overall, 68.2% patients received all four planned cycles, and the cumulative dose delivered for gemcitabine was 8333 mg (83.3% of the planned dose) and cisplatin 248 mg (82.7% of the planned dose). There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 patients (35.6%) and was the predominant hematologic toxicity. Common grade 3/4 non-hematologic toxicities were nausea/vomiting (22.0%), infection (12.3%), and febrile neutropenia (11.4%). Conclusion Cisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerability compared with published data on cisplatin and vinorelbine.

Long-Term Survival of a Patient with Invasive Signet-Ring Cell Carcinoma of the Urinary Bladder Managed by Combined S-1 and Cisplatin Adjuvant Chemotherapy

Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor. The disease usually presents at advanced stages because the cancer progresses rapidly. The only option for effective treatment is radical cystectomy, and no effective chemotherapy has been established for this variant. We report a case of signet-ring cell carcinoma of the urinary bladder with a long-term survival of 90 months owing to radical cystectomy and combination adjuvant chemotherapy with S-1 and cisplatin. To our knowledge, this is the first report to demonstrate the long-term therapeutic activity of combination S-1 and cisplatin adjuvant chemotherapy against invasive signet-ring cell carcinoma of the urinary bladder.

Feasibility of postoperative adjuvant chemotherapy of cisplatin plus vinorelbine for completely resected non-small-cell lung cancer: A retrospective study in Japan

The efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy, such as the combination of CDDP and vinorelbine (VNR), has been established for surgically resected non-small-cell lung cancer (NSCLC). However, the optimal treatment schedule and dosage for CDDP and VNR are unknown. We evaluated patient compliance with and the safety of adjuvant chemotherapy of CDDP at 80 mg/m(2) administered on day 1 plus VNR at 25 mg/m(2) administered on days 1 and 8, every 3 weeks. Medical records of 100 surgically resected NSCLC patients, treated with a combination of CDDP and VNR at the Shizuoka Cancer Center between February 2006 and October 2011, were retrospectively reviewed. Eighty-three (83%) patients completed the planned 4 cycles of CDDP plus VNR and 59 (59%) received the planned doses. Sixty-eight percent of the patients experienced a decreased neutrophil count (grade 3/4 toxicity); 1%, a decreased platelet count; and 4%, febrile neutropenia. No treatment-related deaths were noted in this study. Univariate analysis of the factors influencing patient compliance with this adjuvant chemotherapy showed that neither patient characteristics nor surgical procedure was significantly associated. Our results indicated that adjuvant chemotherapy with CDDP at 80 mg/m(2) administered on day 1 plus VNR at 25 mg/m(2) administered on days 1 and 8, every 3 weeks, was feasible for surgically resected NSCLC cases.

Comparison of S-1 and cisplatin combination versus S-1 adjuvant chemotherapy for advanced gastric cancer.

e14652 Background: Adjuvant chemotherapy demonstrated the efficacy for stage II-III gastric cancer patients in the ACT-GC and CLASSIC trial. However, in the subgroup analysis, stage III patients receiving S-1 monotherapy didn’t report survival benefit unlike the capecitabine/oxaliplatin combination regimen in CLASSIC trial. With the assumption that doublet adjuvant chemotherapy may be more effective for advanced stages of patients, we compared the efficacy of S-1/cisplatin (SP) and S-1 adjuvant chemotherapy. Methods: After curative D2 resection, 274 patients were treated with S-1 monotherapy (98 patients, 80 mg/m2 for 4 weeks, every 6 weeks) or S-1 plus cisplatin (176 patients, S-1 80 mg/m2 day 1-14 and cisplatin 60 mg/m2 day 1, every 3 weeks). Treatment was continued for 12 months in S-1 arm and 6 months in SP arm or until unacceptable toxic effects or disease progression. Results: A total of 65 (66.3%) patients in SP and 118 (67%) in S-1 group completed all the treatment. The relative dose intensity of S-1 was 82% for S-1 and 88% for SP group, respectively. During the early times after the operation, more patients in SP group completed adjuvant treatment. More patients in SP discontinued treatment during the 1st cycle (12.5% S-1 vs 8.5 % SP group) and this trend was consisted thereafter. The progression free survival (PFS) was not reached for both groups. For the stage III patients, 2 year PFS was better for SP group (89%) than S-1 group (80.8%). Among the 23 recurrence, S-1 group (19.8%) demonstrated more frequent recurrence than SP group (12%). In terms of tolerance, hematologic toxicities was more frequent in SP group, therefore, 21% of SP group and 3.4% of S-1 monotherapy had grade 3-4 neutropenia. However, for the non-hematologic toxicity, grade 3-4 anorexia was similar and grade 3-4 stomatitis was more common in S-1 group (2.8% vs 7%) Conclusions: S-1 plus cisplatin adjuvant chemotherapy is effective and tolerable. For the high risk patients, considering favorable compliance and slightly better efficacy, combination treatment may be a good therapeutic option. Further studies for optimal drugs and schedule are warranted.

Tolerability and toxicity of adjuvant cisplatin and gemcitabine for non-small cell lung cancer.

e17504 Background: The combination of cisplatin and vinorelbine is the evidence supported regimen for adjuvant chemotherapy of non-small cell lung cancer (NSCLC). But this doublet has considerable toxicity and unfavorable tolerability, and resulted in poor compliance. Cisplatin and gemcitabine regimen is one of the most active and well tolerated regimens against advanced NSCLC, but its toxicity and tolerability have not been adequately evaluated in the adjuvant setting. Methods: From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m2) and gemcitabine (1250 mg/m2) between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records. Results: A total of 132 patients met the criteria and included in the study, 96 were males (72.7%)and 36 females (27.3%). Median age was 60.5 years (range, 29-75 years), and 41.7% patients were ≥65 years old. Overall, 68.2% received all four planned cycles, and cumulative dose delivered for gemcitabine was 8333 mg (83.3% planned) and cisplatin 248 mg (82.7% planned). There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 (35.6%) patients and was the predominant hematologic toxicity. Common grade 3/4 non-hematologic toxicities were nausea/vomiting (22.0%), infection (12.3%), and febrile neutropenia (11.4%). Conclusions: Cisplatin and gemcitabine are feasible in the adjuvant setting with favorable toxicity profile and superior tolerability compared with published data of cisplatin and vinorelbine.

Sorafenib (Soraf) and bevacizumab (Beva) for recurrent metastatic hepatoblastoma (HB).

9575 Background: Few effective treatment options exist for patients with HB who fail to respond to standard chemotherapeutic agents. Soraf has shown activity in treatment of advanced hepatocellular carcinoma (HCC); its use in HB has not been reported. Beva (combined with other agents) is used to treat several types of metastatic cancers. We report the use of Soraf and Beva in combination for a patient with recurrent metastatic HB recalcitrant to traditional agents. Methods: A 2-year old male with a left-sided abdominal mass and AFP of 33,608 ng/ml had a left hepatectomy to remove a large embryonal HB. Adjuvant chemotherapy of cisplatin, 5-flurouracil, and vincristine was given. The AFP level fell gradually (nadir of 76 ng/ml) after surgery but began to rise during the third cycle of chemotherapy. Computed tomography (CT) of the lung revealed numerous bilateral pulmonary nodules that were proven at biopsy to be HB. Over the next nine months, the following chemotherapeutic regimens were used: 1.Vincristine with irinotecan. 2. Doxorubicin with ifosfamide. 3. Carboplatin with etoposide. 4. Intensive cisplatin and doxorubicin (2 different regimens). 5. Cisplatin plus very high dose acetaminophen with N-acetylcysteine rescue. 6. Erlotinib and Beva for 8 weeks AFP levels continued to rise and serial CT scans demonstrated progressive disease, except for a brief period of stable disease after treatment # 4. Based on the efficacy of Soraf in HCC and the possibility that this tumor was acting more like a

Disease-Free Survival at 2 or 3 Years Correlates With 5-Year Overall Survival of Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival. We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic. Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival. Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.

Squamous cell carcinoma of the breast: a case report

IntroductionPure primary squamous cell carcinoma of the breast is uncommon and it's debated the correct management of this disease.Case presentationA 54-years-old woman presented with signs and symptoms of mastitis of left breast. A palpable well circumscribed and firm mass, measuring about 40 mm, was present in the left lower lateral quadrant. She underwent antibiotic therapy without benefit. She performed an ultrasound and mammographic scan of the left breast. Fine needle aspiration cytology revealed an infiltrative poorly differentiated squamous cell carcinoma. Total body CT scan and bone scan excluded distant metastasis. Subsequently wide local excision of the left breast with ipsilateral axillary lymph nodes dissection was performed. The pathological examination revealed an infiltrative poorly differentiated squamous cell carcinoma of the breast. Adjuvant chemotherapy cisplatin and 5-fluorouracil based was administered. Patient refused locoregional radiotherapy. Twenty-eight months after surgery the patient was disease free.ConclusionsPure primary squamous cell carcinoma of the breast is a rare and aggressive disease often treatment-refractory. An optimal systemic treatment is needed to improve patient's outcome.