Second-line Combination Chemotherapy Research Articles

Clinical features of gestational choriocarcinoma: A retrospective bicentric study.

To investigate the clinicopathological features, prognostic factors, treatment, clinical response, and outcome of gestational choriocarcinoma (GCC). A retrospective review was made of the clinicopathological and survival data of 13 patients who were diagnosed and treated for GCC in two referral centers in Turkey between 1992 and 2020. The median age of patients was 36 years (range, 27-54 years), and seven were ≤39 years. The antecedent pregnancy was a term in nine (69.2%) cases, and the risk score was ≥7 in 11 (84.6%). According to the International Federation of Gynecology and Obstetrics 2009 staging, eight cases were in stage I, two in stage III, and three in stage IV. With the exception of one patient, all the others received combination chemotherapy (CT), and two of those were also treated with radiotherapy. Chemoresistance developed in 50% (6/12), and second-line CT was given to four of these. The overall complete response rate was 69.2%. Four patients died of chemoresistance and disease progression, all of them were with antecedent-term pregnancy, had high scores ≥7, and had metastases. GCC is a unique subtype of gestational trophoblastic neoplasia, which differs from others in terms of poor prognosis, a frequent tendency to early metastasis, and resistance to treatment. To be able to achieve the most efficient therapy and prognosis, histopathology-based risk models should be developed.

The Efficacy of Second-line Chemotherapy for Advanced or Metastatic Urothelial Cancer.

This study aimed to assess the efficacy and toxicity of second-line chemotherapy, especially combination chemotherapy, for advanced or metastatic urothelial cancer. This retrospective analysis included patients who received second-line chemotherapy after disease progression during first-line chemotherapy between January 2009 to May 2018. Progression-free survival (PFS), overall survival (OS) and toxicity associated with second-line chemotherapy were assessed. In total 25 patients received second-line chemotherapy; 21 patients had combination chemotherapy and 4 had single-agent chemotherapy. Median PFS and OS were 3.6 months (range=0.2-23.5) and 11.9 months (range=0.5-29.0), respectively. Twenty patients (80%) exhibited grade 3 or more severe toxicities. PFS and OS benefits of second-line combination chemotherapy corresponded to those of the phase 3 study of pembrolizumab, but adverse events were more severe. Pembrolizumab is potentially a better second-line treatment than combination chemotherapy.

PRODIGE 53-UCGI 30 (SULTAN): A randomized phase II study comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy to systemic chemotherapy alone in patients with liver-only colorectal metastases considered still non resectable after at least two months of systemic induction chemotherapy.

TPS3619 Background: In the first-line setting, current combination chemotherapy (CT) achieve high objective response rates (ORR) ranging from 40% to 80% and leads to complete resection rate (CRR) of colorectal cancer liver metastasis (CRCLM) in 25% to 50% of patients with initially non-resectable CRLM. However, when patients with CRLM are still not amenable to resection after induction CT, ORRs (~5-30%) and CRRs ( < 10%) obtained with second-line systemic CT are much lower. Combining hepatic arterial infusion (HAI) and systemic (SYS) CT for unresectable CRLM lead to high ORR and the potential of cure in the second-line and further setting. Methods: This multicenter randomized phase II trial conducted in 20 centers in France plans to include 140 patients with CRLM still not amenable to a curative intent-treatment after at least two months of first-line induction SYS CT whatever the tumor response. Patients are randomized (1:1) between intensified biweekly regimen combining HAI oxaliplatin (100 mg/m²) and SYS FOLFIRI (leucovorin 400 mg/m², irinotecan 180 mg/m², and 5-FU 2.4 g/m²over 48 h) plus cetuximab 500 mg/m² or bevacizumab 5 mg/kg (according to RAS status and prior response/tolerance to SYS induction CT) or SYS CT alone according to current guidelines. The primary endpoint is to evaluate and compare the curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM in both arms. A gain of 20% in CRR is expected (30% in the experimental arm vs. 10% in the control arm; α 5% [two-sided]; β 20%). Stratification factors at randomization are prior adjuvant or SYS induction oxaliplatin-based CT, tumor response to SYS induction CT, and center. Secondary endpoints include progression-free (overall, hepatic and extrahepatic) and overall survival, ORR, relative change in the sum of longest diameters of RECIST target lesions (DoR) and feasibility/tolerability. Since study start, 3 patients have been enrolled to date (planned accrual period: 3 years). Clinical trial information: NCT03164655.

Molecular classification of tissue from a transformed non-Hogkin\u2019s lymphoma case with unexpected long-time remission

BackgroundThe concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www.hemaclass.org. We expected that such a study could generate therapeutic information and a frame for future individual evaluation of molecular resistance detected at clinical relapse.Case presentationThe patient was diagnosed with a transformed high-grade non-Hodgkin lymphoma stage III and treated with conventional R-CHOP [rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O) and prednisone (P)]. Unfortunately, she suffered from severe toxicity but recovered during the following 6 months’ remission until biopsy-verified relapse. The patient refused second-line combination chemotherapy, but accepted 3 months’ palliation with R and chlorambucil. Unexpectedly, she obtained continuous complete remission and is at present >9 years after primary diagnosis. Molecular studies and data evaluation by principal component analysis, mutation screening and copy number variations of the primary and relapsed tumor, identified a pattern of branched lymphoma evolution, most likely diverging from an in situ follicular lymphoma. Accordingly, the primary diagnosed transformed lymphoma was classified as a diffuse large B cell lymphoma (DLBCL) of the GCB/centrocytic subtype by “cell of origin BAGS” assignment and R sensitive and C, H, O and P resistant by “drug specific REGS” assignment. The relapsed DLBCL was classified as NC/memory subtype and R, C, H sensitive but O and P resistant.ConclusionsThorough analysis of the tumor DNA and RNA documented a branched evolution of the two clinical diagnosed tFL, most likely transformed from an unknown in situ lymphoma. Classification of the malignant tissue for drug-specific resistance did not explain the unexpected long-term remission and potential cure. However, it is tempting to consider the anti-CD20 immunotherapy as the curative intervention in the two independent tumors of this case.

22 Second-line combination chemotherapy with cisplatin, gemcitabine and paclitaxel for the treatment of advanced germ cell tumours

22 Second-line combination chemotherapy with cisplatin, gemcitabine and paclitaxel for the treatment of advanced germ cell tumours

Efficacy of platinum combination chemotherapy after first-line gefitinib treatment in non-small cell lung cancer patients harboring sensitive EGFR mutations.

Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy. Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39-75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9%, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2%, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS. Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS.

Second-Line Therapy of Small-Cell Lung Cancer: Topotecan Compared to a Combination Treatment with Adriamycin, Cyclophosphamide And Vincristine (ACO) - a Single Center Experience.

Background: Randomized trials established topotecan and the combination of adriamycin, cyclophosphamide and vincristine (ACO) as second-line therapy options for small-cell lung cancer. We retrospectively evaluated the outcome of SCLC patients undergoing second-line chemotherapy.Patients and Methods: 92 consecutive patients with a diagnosis of SCLC between 2000 and 2010 were analyzed.Results: 86 patients (93.5%) were evaluable for outcome analysis. All patients diagnosed with limited disease (LD) SCLC received platinum-based chemotherapy as first-line treatment. 69 patients (98.6%) diagnosed with extensive disease (ED) SCLC received first-line palliative chemotherapy. In the total cohort, the median overall survival (OS) was 10.3 months (19.2 months and 9.2 months for LD-SCLC and ED-SCLC, respectively). 42 patients received second-line therapy (ACO in 47.6% and topotecan in 31.0% of patients, respectively). Eight patients (19.0%) were re-challenged with platinum/etoposide. Neither the overall response rate (52.9% vs. 22.2%; p=0.128) nor progression-free survival (2.4 vs. 2.4 months; p=0.794) or OS (5.5 vs. 5.0 months; p=0.997) were significantly different between ACO and topotecan. ACO-treated patients showed a trend towards a longer duration of inpatient care.Conclusion: We showed similar outcomes as reported in clinical trials. Second-line combination chemotherapy with ACO did not show superiority to intravenous topotecan, but was associated with a clinically relevant longer hospitalization time.

Second-line combination chemotherapy with docetaxel and nedaplatin for metastatic or recurrent squamous cell carcinoma of the esophagus refractory to chemotherapy with 5-fluorouracil plus cisplatin

Background There is no standard second-line chemotherapy regimen after failure of the standard 5-fluorouracil and cisplatin in the treatment of esophageal cancer. We retrospectively investigated the efficacy and toxicity of combination chemotherapy using docetaxel and nedaplatin for patients with metastatic or recurrent squamous cell carcinoma of the esophagus refractory to prior chemotherapy with 5-fluorouracil and cisplatin, and evaluated the prognostic significance of clinical factors in these patients.

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.

Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99

BackgroundThe second-line chemotherapeutic treatment for metastatic urothelial cancer (UC) after failure of cisplatin-based first-line therapy needs to be improved. Based on encouraging phase II data of gemcitabine and paclitaxel (Taxol) (GP), this trial was designed to compare a short-term (arm A) versus a prolonged (arm B) second-line combination chemotherapy of GP. Patients and methodsOf 102 randomized patients, 96 were eligible for analysis. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rates (ORR) and toxicity. ResultsNeither OS [arm A: 7.8 (95% CI: 4.2–11.4), arm B: 8.0 (95% CI: 4.9–11.1) months] and PFS [arm A: 4.0 (95% CI: 0–8.0), arm B: 3.1 (95% CI: 1.9–4.2) months] nor ORR (arm A: 37.5%, arm B: 41.5%) were significantly different. On prolonged treatment, more patients experienced severe anemia (arm A: 6.7% versus arm B: 26.7% grade III/IV anemia; P = 0.011). In six patients, treatment was stopped during the first cycle due to disease progression or toxicity. Two patients died due to treatment-related toxic effects. ConclusionDue to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting, it was not feasible to deliver a prolonged regimen. However, a high response rate of ∼40% makes GP a promising second-line treatment option for patients with metastatic UC.

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.

Chemo-resistant gestational trophoblastic neoplasia, 5-years experience of Mansoura University Hospital, Egypt

Introduction: Gestational trophoblastic neoplasia (GTN), is recognized as the most curable gynaecologic malignancy. However, many cases are resistant to first line chemotherapy. Objective: The aim of the study is to report our 5 years experience in the management of GTN cases with special stress on the chemo-resistant cases. Methods: The study was performed through reviewing the records of 51 patients who were diagnosed as GTN during the period from 1/1/2006 to 31/12/2010 in Mansoura University Hospital, Egypt. Results: Resistance to methotrexate therapy was reported in 15.15% of low risk cases and received etoposide or cisplatinum/etoposide. Sixty percent of high risk cases were resistant to MAC combination and received salvage chemotherapy or hysterectomy. There was significant correlation between patient response and initial B-hCG, as well as WHO risk score (P value = 0.001 in both) but correlations with age, parity, type of antecedent pregnancy, and histopathology were non significant (p = 0.95, 0.53, 0.47& 0.83 respectively). Conclusion: Low risk GTN cases who were resistant to methotrexate monotherapy received etoposide or cisplatinum/etoposide as a second-line therapy. High risk GTN cases who were resistant to MAC combination received second-line combination chemotherapy and/or hysterectomy. WHO risk score and initial B-hCG were correlated to resistance to first line chemotherapy.

Metastatic Colorectal Cancer: Focus on Panitumumab

Biologic agents designed as targeted therapy are at the forefront of research in the field of colorectal cancer. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) represent one such form of treatment, and the novel agent panitumumab is the first fully-human monoclonal antibody developed in this class. This drug is generally well-tolerated, with skin toxicities similar to those associated with other EGFR inhibitor therapies as the primary adverse effect. Efficacy has been evaluated in multiple settings, and panitumumab has demonstrated significant therapeutic effect both as monotherapy, as well as part of first- and second-line combination chemotherapy regimens. Panitumumab has also played a pivotal role in establishing the importance of biomarker science in the field of colorectal cancer and the whole of oncology. Studies demonstrating lack of therapeutic response to the agent in the setting of KRAS mutation led to the first indication of an agent based on genetic characteristics. Current and ongoing studies will continue to define panitumumab and determine its role in the treatment of colorectal cancer. This review will present background information on this therapeutic agent and explore present and future directions.

Docetaxel combined with oral etoposide as second-line treatment for advanced gastric carcinoma after failure of platinum- and fluoropyrimidine-based regimens

Platinum, antracyline, and fluoropyrimidine combination chemotherapy has been widely used as a first-line treatment for advanced gastric cancer (AGC). In the present study, we determined the efficacy and the safety of docetaxel and oral etoposide as second-line combination chemotherapy after failure of commonly used combination regimens in AGC. Patients with histologically proven gastric cancer and measurable metastatic disease received docetaxel 75 mg/m(2) as a 1-h intravenous infusion on day 1, and oral etoposide 50 mg/m(2) once daily on days 1-5, every 3 weeks until disease progression or unacceptable toxicities. Between June 2006 and September 2008, 32 patients, of median age 60 years (range 32-77 years) were included in the study. Overall response rate was 9.4% and 31.3% of patients achieved a stable disease. Median progression-free survival was 3 months (95% CI, 2.5-3.5). Median overall survival was 6 months (95% CI, 3.8-8.2) with 16.9% 1-year survival rate. Grade 3-4 toxicities included neutropenia (28.8%), febrile neutropenia (18.8%), thrombocytopenia (3.1%), nausea and vomiting (15.6%), diarrhea (9.4%), and mucositis (6.2%). Docetaxel and oral etoposide combination was moderately effective and safe in appropriately selected AGC patients after failure of platinum- and fluoropyrimidine-based combination regimens.

Second-line therapy in bladder cancer

To review new developments in second-line treatment for transitional cell carcinoma of the urinary bladder focusing on advances and findings within the last year. So far no standard therapy has been established for pretreated patients with transitional cell carcinoma. Prognostic and predictive factors for response and outcome in pretreated patients have been studied retrospectively and will help to identify those who might benefit from intensive therapy and those who would rather improve their quality of life with best supportive care. Single-agent chemotherapy in this setting provided low response rates, short progression-free and overall survival. Vinflunine, a novel vinca-alkaloid, and best supportive care had a modest, but still significant benefit at a very moderate toxicity rate in a randomized phase III trial. As for second-line combination chemotherapy, response rates as well as potential toxicities are higher and the progression-free survival and overall survival benefits are still poorly understood. New chemotherapeutics and approaches like metronomic chemotherapy and novel agents are under investigation. With vinflunine there is reasonable hope for a new standard chemotherapy in second-line management of transitional cell carcinoma. However, due to the reported results with single agents and combination chemotherapy, treatment within clinical trials is still the best choice in patients progressing after first-line chemotherapy.

Second-Line Combination Chemotherapy with Docetaxel and Nedaplatin for Cisplatin-Pretreated Refractory Metastatic/Recurrent Esophageal Squamous Cell Carcinoma

There is an urgent need for an effective second-line chemotherapy regimen after failure of the standard cisplatin and 5-fluorouracil therapy. This study investigated the efficacy and toxicity of the combination of docetaxel (30 mg/m2) during a 1-hour infusion, followed by nedaplatin (50 mg/m2) during a 2-hour infusion (both drugs were administered on day 1 as an outpatient regimen and repeated every 2 weeks) as second-line chemotherapy for patients with cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma after surgery. Forty-six of the 48 patients (95.8%) were assessable for response. Partial response was confirmed in 13 of 48 cases yielding a response rate of 27.1% (95% confidence interval [CI], 14.5-39.7%). The median overall time to progression and overall survival was 3.1 months (95% CI, 2.3-3.9 months) and 5.9 months (95% CI, 3.9-7.8 months), respectively. The estimate of overall survival at 12 months was 16.7% (95% CI, 6.1-27.2%). Grade 3 anemia leucopenia, grade 4 anemia leucopenia and neutropenia were detected in only 4 (8.7%), 8 (17.4%), and 9 patients (19.6%), respectively. The combination chemotherapy of docetaxel and nedaplatin in the outpatient setting is well tolerated and useful as second-line chemotherapy for cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma.

Phase II study of paclitaxel combined with capecitabine as second-line treatment for advanced gastric carcinoma after failure of cisplatin-based regimens

To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m(2) twice daily (1,650 mg/m(2) per day) on days 1-14 and paclitaxel 175 mg/m(2) by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41-84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2-55.7%) with one complete response and 42.3% (95%CI = 17.2-55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4-4.5 months). Median overall survival was 7.5 months (95%CI = 6-10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11-18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts.

Nondysgerminomatous ovarian tumors: Clinical characteristics, treatment, and outcome: A case-controlled study

Objective The aim of this study is to assess the response of patients with nondysgerminomatous ovarian germ-cell tumors (NDOGCT) to platinum-based chemotherapy and to determine association of prognostic factors to relapse of disease. Methods We retrospectively reviewed 21 patients who had surgical resection of nondysgerminomatous ovarian germ-cell tumors (NDOGCT) and received adjuvant chemotherapy in Vali-e-Asr Hospital, Tehran, Iran during 1997–2004. The median age at presentation was 18 years and the median follow-up was 20 months. Histological type of tumors included the following: immature teratoma ( n = 7), mixed germ-cell tumor ( n = 7), yolk sac tumors ( n = 4), and embryonal carcinoma ( n = 3). Distribution by stage at the time of surgery was as follows; stage I ( n = 10), stage III ( n = 6), and stage IV ( n = 5). Results Sixteen patients underwent unilateral salpingo-oophorectomy and 5 patients underwent cystectomy. After the initial surgery, 13 patients immediately received chemotherapy and the other 8 patients received chemotherapy at a median time of 5.5 months (range, 1–40 months). Postoperative chemotherapy included the following: bleomycin, etoposide, and cisplatin ( n = 17); vincristine, actinomycin-D, and cyclophosphamide ( n = 2); methotrexate, etoposide, and cisplatin ( n = l); and cisplatin ( n = l). Thirty-one percent of the patients suffered a relapse after platinum-based combination chemotherapy. The median disease-free survival was 40 months and the median overall survival was 50 months. The 5-year survival rate was 39%. Conclusions This study showed that stage at the initial surgery, residual disease and the interval from initial diagnosis to the start of chemotherapy were possible prognostic factors for relapse. Also, our study indicates that there may be a role for aggressive cytoreductive surgery in advance NDOGCT, and a need for second-line combination chemotherapy.

New therapeutic options in metastatic colorectal cancer

15107 Background: The median overall survival (OS) of metastatic colorectal cancer (mCRC) patients (pts) treated with first- and second-line combination chemotherapy now extends to more than 18 months in some countries. The aim of this study is to compare the overall survival of pts with mCRC in two different years using our database. Methods: 97 patients diagnosed of mCRC during 2002 and 2005 were included in the study. In 2002 pts received only 5-Fu or capecytabine during the palliative treatment (37% of pts). In 2005 pts (63%) oxaliplatin-based therapy in the first line and FOLFIRI in 2nd line of therapy most often received. All pts were in good condition (WHO 0 or 1). In 23% of pts metastasectomy as part of palliative treatment was performed. Patients characteristics is as follow: male/female ratio: 69/31; colon/rectum: 53/47, mean of age: 59 (range 22–77 years). Location of metastatic lesions: liver - 57%, soft tissue - 41%; lungs - 16%, bone - 4%. The 49% of pts were diagnosed as primary stage IV. Survival curves were constructed according to the Kaplan-Meier method and compared by log-rank analysis Results: The median of OS for the whole group was 14 months. The median of OS in 2002 (pts who received only 5-Fu or capecytabine during the palliative treatment) was 8 months and in 2005 -18 months (p=.00014). Similarly the median of OS this part of pts (43%), who received only 1 line of chemotherapy was significantly shorter (8.5 month) than the median of OS this group of pts (57%), who received at least 2 lines of chemotherapy (19 month) p =.00049. The relevant condition of increasing the median of OS was the possibility of metastasectomy conducting (32 vs. 11 month; p <.0001). Conclusions: A positive CRC mortality trend was observed. The influencing factors were related with the use of new antineoplastic agents and possibility to perform of metastasectomy (especially liver metastatic lesions). No significant financial relationships to disclose.

Second-line combination chemotherapy: A phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic hormone-refractory prostate cancer (HRPC) refractory to docetaxel-based therapy

5151 Background: Mitoxantrone and prednisone (MP) and ixabepilone (Ix) both have modest activity as single agents for 2nd-line chemotherapy in docetaxel-refractory patients with HRPC and have demon...