Combination Chemotherapy In Patients Research Articles

Abstract 3705: Multicenter phase II clinical trial of gemcitabine and liposomal paclitaxel combination chemotherapy in patients with advanced biliary cancer

Abstract OBJECTIVE: Advanced biliary tract cancer is associated with a poor prognosis due to wide resistance to chemotherapeutic agents. This phase II clinical trial was conducted to determine the safety and efficacy of weekly gemcitabine and liposomal paclitaxel (Genexol-PM®) in patients with unrectable or metastatic biliary cancer. METHODS: The eligibility criteria were patients 1) with pathologically proven unresectable or metastatic biliary cancer, 2) with an ECOG performance status 0 to 2, 3) aged more than 18, 4) with measurable lesions, 5) with adequate hematologic, renal and liver functions, and 6) who provided written informed consent. Each treatment cycle was consisted of gemcitabine 1000 mg/m*2 and liposomal paclitaxel 100 mg/m*2 on days 1, 8 followed by rest perioid of 14 days. It was repeated until the appearance of disease progression or unacceptable toxicity up to maximal 9 cycles. The primary end point of this study was reponse rate, and secondary end points included toxicity, progression free survival and overall survival. RESULTS: Thirty five patients were enrolled; median age was 63 years; male (n=30) and female (n-10). The median number of cycles administered was 3.5 (range, 1-10). Thirty patients were assessable for efficacy. Nine partial responses and 16 stable diseases were confirmed. Giving an overall response rate was 35.6% and disease control rate was 55.6% in per-protocol population. Median overall survival was 12.3 months (95% CI: 5.79-18.74) and median progression free survival was 4.07 months(95% CI: 3.12-5.01). The most frequent adverse events (AE) of all grades were anemia and neutropenia (n=17) followed by leucopenia (13). Grade 3/4 hematologic AEs: anemia (n=6), neutropenia (n=11), thrombocytopenia (n=1). Grade 3/4 non-hematologic AEs: elevated liver function tests (n=3), hyperbilirubinemia (n=1) hyponatremia (n=1). CONCLUSION: Weekly gemcitabine combined with liposomal paclitaxel appears to be effective against advanced biliary cancers. Further randomized trials are needed to confirm this finding. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3705. doi:1538-7445.AM2012-3705

Bevacizumab and etoposide combination chemotherapy in patients with recurrent malignant gliomas who failed bevacizumab

Bevacizumab is the current standard of care treatment for recurring malignant glioma patients. However, most of the tumors become resistant to bevacizumab, and there is no standardized, effective chemotherapy for the malignant glioma patients after bevacizumab failure. Retrospective chart review was performed in order to identify the malignant glioma patients treated with oral, metronomic etoposide in combination with bevacizumab after being diagnosed with progressive disease while on bevacizumab. This review was approved by the Institutional Review Board (IRB) of the University of California, Irvine. Six malignant gliomas patients met the inclusion criteria. The median progression-free survival (PFS) for the anaplastic astrocytoma (AA) patients was eight months, and the overall survival was 28 months. The two Glioblastoma Multiforme (GBM) patients showed tumor progression after four to eight weeks of treatment with bevacizumab and etoposide, and died within four months of beginning the etoposide/bevacizumab regimen. In this limited study, patients with AA demonstrated prolonged control on combination treatment with bevacizumab and oral etoposide, despite initial tumor progression on bevacizumab. These results may warrant further investigation on a prospective clinical trial of this combination in AA patients who developed resistance to bevacizumab.

Comparing the treatment outcomes between unresectable and recurrent cases receiving gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer: Pooled analysis of two prospective studies.

331 Background: We previously conducted two prospective studies (phase II study and randomized phase II study) of gemcitabine (GEM) and S-1 combination chemotherapy. The purpose of this study was to clarify the difference of treatment outcomes between unresectable and recurrent cases receiving GEM/S-1 combination chemotherapy in patients with advanced biliary tract cancer. Methods: The data of two prospective studies were combined for the analysis. In these studies, GEM was administered intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 15, repeated every four weeks. S-1 was administered orally at a dose of 40 mg/m2 b.i.d. on days 1-14. Tumor response was assessed every two cycles using RECIST version 1.0. The treatment was continued until disease progression, unacceptable toxicity or patient refusal occurred. Results: Fifty-five unresectable cases and ten recurrent cases were enrolled in this analysis. Patient characteristics were similar between each group except the baseline sum of longest diameter, which was used as a measurement of tumor volume (unresectable 9.0 cm vs recurrent 2.8 cm). Response rates of unresectable and recurrent cases were 25.5% and 40.0%, respectively. Dose intensities of each group were statistically different (gemcitabine 96.8% vs 83.5%, p=0.03; S-1 91.8% vs 75.9%, p=0.03). The median time-to-progressions of unresectable and recurrent cases were 5.7 months and 8.7 months, respectively (p=0.14). The overall survivals of each group were 9.6 months and 16.1 months (p=0.10). Conclusions: In recurrent cases, tumor volume was smaller and dose intensity was lower than that of unresectable cases. Recurrent cases showed better treatment outcome comparing to unresectable cases. Therefore, unresectable and recurrent cases should be analyzed separately in the future study.

Retrospective analysis of hepatitis B virus reactivation after rituximab combination chemotherapy in patients with B-cell lymphoma

The aim of the study was to investigate the reactivations of hepatitis B virus (HBV) after rituximab-containing chemotherapy in patients with B-cell lymphoma with surface antigen of hepatitis B virus (HBsAg)-positive, or hepatitis B core antibody (HBcAb)-positive. A retrospective study of HBV-related markers was performed before and after rituximab-containing treatment in 189 consecutive patients with CD20-positive B-cell lymphoma. Among the 189 non-Hodgkin’s lymphoma (NHL) patients who received rituximab combination chemotherapy, 31 (16.6%) were HBsAg positive and 82 (43.9%) HBsAg negative/HBcAb positive, and 76 were HBsAg and HBcAb negative. Of the 31 HBsAg positive patients, 3 (9.7%) experienced reactivation of HBV. The prevalence of HBV reactivation was 4.0% (1/25) in patients who received prophylactic antiviral treatment and 33.3% (2/6) in those who did not receive prophylactic antiviral treatment (P = 0.032). Prophylactic antiviral treatment decreased the rate of HBV reactivation. Among the 82 HBsAg negative/HBcAb positive patients, 1 (1.2%) experienced HBV reactivation leading to serious hepatitis. Our experience indicates that rituximab-based therapy may cause serious HBV-related complications and even death in HBsAg-positive patients. Preemptive use of antiviral treatment enabled successful management of HBV reactivation. In HBsAg-negative and HBcAb-positive lymphoma patients the prevalence of HBV reactivation is low (1.2%). Close monitoring HBV until at least 6 months after anticancer therapy is required, prophylactic antiviral therapy needs to be evaluated further.

Docetaxel/irinotecan combination chemotherapy in platinum/taxane-refractory and -resistant ovarian cancer: JGOG/WJGOG Intergroup Study

The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment. Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m(2) (day 1) and irinotecan 60 mg/m(2) (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease. Thirty-two patients were available for determination of the clinical response. The overall response rate [complete response (CR) + partial response (PR)] was 6.3%, and the disease control rate (CR + PR + stable disease) was 34.4%. Among the 23 patients with resistant tumor, the disease control rate was 47.8%. Ten patients with refractory tumor showed a 10% disease control rate. The median progression-free interval was 12.1 weeks and the median overall survival time was 45.3 weeks. The major toxic adverse effect was neutropenia (grade 4, 56.1%), but the incidence of neutropenic fever was less frequent (4.9%). Neurotoxicity and gastro-intestinal toxicity were mild. Among our patients, a combination of docetaxel and irinotecan was well tolerated. However, this combination may not be a beneficial option for patients with platinum-refractory and -resistant ovarian cancer in terms of response rate and survival.

Comparative Outcomes of Pure Squamous Cell Carcinoma and Urothelial Carcinoma With Squamous Differentiation in Patients Treated With Radical Cystectomy

We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma. We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression. Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p ≤0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p ≤0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002). There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma.

MP-15.20 Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients with Disseminated Nonseminomatous Testicular Tumors: Is a Post-Chemotherapy Retroperitoneal Lymphadenectomy Needed After Complete Remission?

MP-15.20 Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients with Disseminated Nonseminomatous Testicular Tumors: Is a Post-Chemotherapy Retroperitoneal Lymphadenectomy Needed After Complete Remission?

A phase II study of cisplatin plus S-1 in patients with carcinomas of unknown primary site.

e13620 Background: Carcinomas of unknown primary site (CUP) represent a group of heterogeneous tumors and accounts for about 5% of all cancer patients (pts). The prognosis of CUP is generally poor with a median overall survival time (OS) of 4 to 6 months, and no standard chemotherapy has been established. S-1 is a new oral fluoropyrimidine and shows broad efficacy for many carcinomas. Therefore, we conducted a phase II study of novel combination chemotherapy using cisplatin (CDDP) plus S-1 in pts with CUP to evaluate the efficacy and safety. Methods: The treatment schedule included CDDP given intravenously on day 8, and S-1 given orally twice a day on days 1-21, every 5 weeks. The primary endpoint was objective response rate, and secondary endpoints included safety, OS, and 1-year survival rate. Results: A total of 46 chemotherapy naïve pts were enrolled. Median age of pts was 63 years (range 31-84). There were twenty-five male. Twenty-three pts had adenocarcinoma, fourteen had squamous cell carcinoma, three had poorly differentiated carcinoma, and three had poorly differentiated adenocarcinoma. Eighteen pts presented with nodal metastasis only, and twenty-two with nodal and multiple organ metastasis. The median number of courses was four. The overall response rate and the disease control rate were 41.3% and 80.4%, respectively. (CR/PR/SD/PD/NE; 2/17/18/7/2) The median progression-free survival time and the overall survival time were 7.5 months and 17.4 months, respectively. The most common grade 3 or worse adverse events were hematologic and non-hematologic toxicities were generally mild. Neutropenia, thrombocytopenia, and febrile neutropenia occurred in 28.3%, 13%, and 2.2%, respectively. Conclusions: This study demonstrates the activity of CDDP plus S-1 combination chemotherapy in patients with CUP. Updated response rate, safety data, and OS data will be presented.

Oxaliplatin, 5-FU, and leucovorin (FOLFOX) in advanced biliary tract cancer.

4106 Background: There is no standard palliative chemotherapy regimen in biliary tract cancers (BTC). Fluoropyrimidine or gemcitabine, with or without platinum, are most frequently used. The purpose of this prospective multicenter phase II study was to evaluate the efficacy and safety of FOLFOX-6(5-FU/LV plus oxaliplatin) combination chemotherapy in patients with advanced BTC. Methods: Eligible criteria included pathologically or cytologically confirmed biliary adenocarcinoma, unresectable or metastatic BTCs with at least one measurable lesion, no previous palliative chemotherapy, age ≥ 18, performance status ≤ 2, adequate organ function and no clinically significant cardiovascular disease. 89.8% patients had metastatic disease. All patients received FOLFOX-6 (oxaliplatin 85mg/m2 and folinic acid 400 mg/m2 on day 1 follwed by a 5-FU bolus 400 mg/m2 and 46-h infusion 2400 mg/m2 every 2 weeks) until progression of disease or unacceptable toxicities. Tumor response was evaluated each after four treatment cycles using the RECIST. Results: 49 patients were enrolled in this phase II study from May 2008 to Aug 2010. Medain age was 60.14 years (range 35-80), male/female=27/12, ECOG performance status 0/1/2 = 23/21/5. The primary tumor site was 14 patients in gallbladders, 28 patients in intrahepatic cholangiocarcinoma, and 7 patients in extrahepatic cholangiocarcinoma. 44 patients showed metastatic disease at baseline. Total chemotherapeutic cycles were 210 and 4.29 cycles were performed each person. Treatment related grade 3/4 toxicities included (number of cycles) diarrhea (2), neutropenia (10), neutropenic fever (2), anemia (1), thrombocytopenia (2), nausea (1) and pneumonia (1). Overall response rate was 16.3% and overall disease control rate was 61.7%. The median TTP was 3.83 months (95%CI, 3.45-5.68 months) and the overall survival was 10.77 months (95%CI, 7.92-13.62 months). No treatment related deaths occurred during the study. Conclusions: This results suggest that FOLFOX-6 would be an effective and well-tolerated chemotherapy regimen for Korean patients with advanced BTC.

Second-Line Combination Chemotherapy with Vinorelbine and Capecitabine in Patients with Advanced Breast Cancer Previously Treated with Anthracyclines and/or Taxanes

Objective: This phase II study was designed to evaluate the effects of vinorelbine (VRL) and capecitabine (CAP) as second-line combination chemotherapy in patients with advanced breast cancer (ABC) previously treated with anthracyclines and/or taxanes. Methods: Treatment consisted of VRL 25 mg/m² administered on days 1 and 8 of a 21-day treatment cycle, along with oral CAP 825 mg/m² twice daily for 14 days, followed by 7 days of rest. Results: 50 patients were enrolled and 48/50 (96.0%) patients were assessable for response. The median time to progression (TTP) and overall survival (OS) of the patients were 5.0 (95% confidence interval, CI, 2.1–7.9 months) and 12.0 months (95% CI, 8.0–16.0 months), respectively. The objective response rate was 26.0% (95% CI, 13.8–38.2%) with 1 confirmed complete response and 12 partial responses. The most frequent hematological adverse event was neutropenia of grade 3 and 4 in 5 (10.4%) and 2 patients (4.2%), respectively. Grade 3 stomatitis, asthenia, and diarrhea were observed in 1 (2.1%), 2 (4.2%) and 3 (6.3%) patients, respectively. Conclusion: The combination of VRL and CAP is feasible as second-line chemotherapy in patients with ABC previously treated with anthracyclines and/or taxanes, with efficacy being comparable to other available combination regimens.

A phase II study of combination chemotherapy with capecitabine and cisplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck

BackgroundThe purpose of this study was to assess the efficacy and toxicity of capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and methodsThe chemotherapy regimen consisted of capecitabine 1250 mg/m2 orally twice a day on day 1 to day 14 and cisplatin 60 mg/m2 i.v. on day 1. Each cycle was repeated every 3 weeks up to a maximum of six cycles. ResultsBy intent-to-treat analysis, the overall response rate was 50% [complete response, 0/36; partial response, 18/36; 95% confidence interval (CI) 32% to 67%]. The median progression-free survival was 3.7 months (95% CI 2.1–5.3 months), and the median response duration was 4.9 months. The median overall survival and 1-year survival rate were 10.3 months (95% CI 8.5–12.1 months) and 43.3%, respectively. The common grade 3 or 4 nonhematologic adverse events were anorexia (8.8%), fatigue (4.4%), diarrhea (4.4%), stomatitis (3.6%), and the hand–foot syndrome (1.5%). The most common grade 3 or 4 hematologic adverse event was neutropenia (14.6%), followed by anemia (1.5%). There was no treatment-related death. ConclusionThe XP combination regimen has antitumor activity and acceptable safety profile in patients with metastatic or recurrent SCCHN.

Phase II study of fixed-dose-rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced bile duct cancer: Daegu Gyeoungbuk Oncology Group.

280 Background: This phase II study evaluated efficacy of fixed dose rate (FDR) infusion of gemcitabine (10mg/m2/min) and UFT combination in chemo-naïve patients with advanced bile duct cancer. Methods: This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received the FDR gemcitabine 1,000mg/m2 for 3 consecutive weeks and UFT 400 mg/m2 on days 1-21. The cycle was repeated every 28 days. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response rate. Secondary end points included clinical benefit response (CBR), safety, progression-free survival (PFS), and overall survival (OS). Clinical characteristics including four single nucleotide polymorphisms in DNA repair genes (RecQ1, RAD54L, XRCC1, ATM) were evaluated whether these influence the overall survival. Results: Between December 2006 and February 2008, fifty-one patients were enrolled, with a median age of 58 years. The majority of patients (76%) had intra-hepatic disease. Fourteen patients (27%) had a RECIST investigator-assessed, partial response (PR); disease control rate (PR + stable disease) was 55%. CBR was 14% among 37 evaluable patients. Hematologic toxicity was main grade 3 or 4 treatment-related adverse events. Median PFS was 4.0 months (95% CI, 2.9 to 5.1 months). Median OS was 7.0 months (95% CI, 3.5 to 10.5 months). Intrahepatic disease, poor performance, and, XRCC1 R194W C/C type were predictive markers of poor overall survival. Conclusions: FDR gemcitabine and UFT demonstrated apparent activity in patients with advanced bile duct cancer. However, this activity did not translate to prolong survival. The location of disease, performance status, and, polymorphic variants of DNA repair genes may affect clinical outcome of patients with advanced bile duct cancer. No significant financial relationships to disclose.

Gemcitabine and cisplatin combination regimen in patients with anthracycline- and taxane-pretreated metastatic breast cancer

This study was conducted to evaluate the response rate of gemcitabine and cisplatin as second-line combination chemotherapy in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Thirty-eight eligible women with measurable disease and anthracycline- and taxane-pretreated MBC were enrolled. The chemotherapy treatment consisted of gemcitabine (1,250 mg/m(2) by intravenous infusion over 30 min on days 1 and 8) and cisplatin (75 mg/m(2) by intravenous infusion over 1 h on day 1), which were administered every 21 days. Thirty-seven of 38 (97.4%) of patients were assessable for response. The objective response rate was 42.1% (95% CI, 26.4-57.8%) with 16 partial responses. The median time to progression (TTP) and overall survival (OS) for all patients were 5.4 months (95% CI, 2.7-8.1 months) and 13.9 months (95% CI, 9.4-18.4 months), respectively. The most frequent hematologic-related adverse events were grade 3/4 leucopenia and thrombocytopenia, observed in 10 patients (27.0%) and 11 (29.7%), respectively. Grade 3 stomatitis was observed in 3 (8.1%) patients. No grade 4 nonhematologic toxicity was observed in this study. No treatment-related deaths occurred during the study. In conclusion, the combination of gemcitabine and cisplatin is a safe and tolerable regimen as second-line combination for patients with anthracycline- and taxane-pretreated MBC.

Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes

PurposeThe role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes.MethodsThirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m2 of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes).ResultsThe median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade ≥3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred.ConclusionThese results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.

A Phase II Study of Irinotecan, Continuous 5-Fluorouracil, and Leucovorin (FOLFIRI) Combination Chemotherapy for Patients With Recurrent or Metastatic Gastric Cancer Previously Treated With a Fluoropyrimidine-Based Regimen

A phase II study was carried out to assess the efficacy and toxicity of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) for the treatment of patients with metastatic or recurring gastric cancer previously treated with fluoropyrimidine-based chemotherapy. Eligible patients were those who had metastatic gastric cancer previously treated with a fluoropyrimidine-based chemotherapy regimen or had disease recurrence within 6 months of completing adjuvant fluoropyrimidine-containing chemotherapy. Participants received irinotecan (150 mg/m² on day 1) and leucovorin (LV; 20 mg/m² on days 1-2) followed by continuous infusion of 5-FU (1500 mg/m² on days 1-2), every 2 weeks. Between April 2006 and March 2008, 33 patients were enrolled in the study. FOLFIRI served as a second-line treatment in 27 patients, third-line treatment in 4 patients, and fourth-line treatment in 2 patients. The patients had a median age of 60 years (range, 40-75) and underwent 132 cycles of chemotherapy, with a median of 3 cycles (range, 1-15) per patient. The response rate was 18.2%, and the disease control rate was 36%. Median overall survival was 5.1 months (95% confidence interval, 3.74-6.45), and median time to progression was 2.3 months (95% confidence interval, 1.81-2.78). The major grade 3-4 toxicity was neutropenia (45.4%). Combination chemotherapy with irinotecan, 5-FU, and LV is feasible in gastric cancer patients previously treated with fluoropyrimidine-based chemotherapy.

Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710).

• To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour. • This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. • For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. • Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage. • There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67-1.21; P= 0.48). • There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09). • Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.

CK5/6, EGFR, Ki-67, cyclin D1, and nm23-H1 protein expressions as predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced triple-negative breast cancers (TNBCs). Forty-one patients (18.6%) among 220 breast cancer patients were identified as TNBCs from March 2006 to 2009 were included in this prospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), CK5/6, epidermal growth factor receptor (EGFR), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). A total of 180 cycles were administered with the median number of four cycles per patient (range, 4-6). The pCR rate was 34.1% (95% CI, 19.6-48.6%). In univariate analysis, early T stage, clinical response after 2 cycles, negative basal-like, negative EGFR, high Ki-67 proliferation index, and positive nm23-H1 were found to be significantly predictive of a pCR (P = 0.010, 0.040, 0.007, 0.001, 0.019, and 0.010, respectively). Basal-like status and nm23-H1 status were significant for pCR on multivariate analysis (P = 0.004 and 0.031, respectively). Basal-like status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with TNBCs.

Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer

BackgroundsCisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers.MethodsIn 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS).ResultsThe median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin levelConclusionAll of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.

Topotecan and ifosfamide systemic chemotherapy for CNS involvement of solid tumors

The prognosis of patients with CNS involvement of solid tumors is poor. In these patients, systemic chemotherapy has a theoretical advantage of concurrent treatment of systemic disease and reduced risk of neurotoxicity. Here, we report on the efficacy and toxicity of topotecan/ifosfamide (TOPO/IFO) combination chemotherapy in patients treated for CNS involvement of different solid malignancies. Fourteen patients with CNS manifestations (seven with brain metastases, two meningeal carcinomatosis, and five both) of solid tumors (seven with breast cancer, six lung cancer, and one unknown primary cancer) received TOPO/IFO treatment. Eleven patients each were pretreated with 1-6 systemic therapy regimens and whole-brain irradiation. Patients received a total of 34 (median 2) TOPO/IFO cycles. TOPO dosage was 3.6 mg/m(2) (1.2 mg/m(2), days 1-3) and IFO dosage 3,000 mg/m(2) (1,500 mg/m(2), days 1-2) per cycle. Of 12 patients with brain metastases, one patient had partial remission, three stable disease, two progressed, and six had no radiologic CNS response evaluation. Response of meningeal carcinomatosis was found in two and progressive disease in two (three patients not evaluated). Neurologic improvement or stabilization was observed in six of twelve evaluable patients. No systemic tumor response was seen in seven evaluated patients. Grade 3/4 toxicities in eleven evaluable patients were leukopenia (n = 9), infection (n = 6), and thrombopenia (n = 5). Median time to treatment failure was 43 days and median overall survival 107 days. Symptom control was frequently achieved with TOPO/IFO systemic chemotherapy despite a low objective response rate. The feasibility of this treatment is impaired by severe hematotoxicity.

ER, PgR, HER-2, Ki-67, topoisomerase IIα, and nm23-H1 proteins expression as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC) One hundred and twelve consecutive patients with clinical stage III LABC who had received NCT with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), Topoisomerase II alpha (Topo-II), and nm23-H1 were detected by immunohistochemistry (IHC). A total of 361 cycles were administered with the median number of three cycles per patient (range, 2-6). The pCR rate was 9.8% (95% CI, 4.3-15.3%). In univariate analysis, poor tumor differentiation, both negative of ER/PgR, negative Topo-II, and positive nm23-H1 were found to be significantly predictive of a pCR. ER/PgR status and nm23-H1 were significant for pCR on multivariate analysis (P = 0.006 and 0.025, respectively). ER/PgR status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with LABC.