scholarly journals DERN CONTROL POINT INHIBITORS AND THEIR POSSIBILITIES FOR THE THERAPY OF METASTATIC UROTELIAL CANCER

2020 ◽  
Vol 6 (5(74)) ◽  
pp. 4-8
Author(s):  
M.N. Tillyashajhov ◽  
S.V. Kamyshov ◽  
E.V. Bojko
Keyword(s):  
Overall Survival ◽  
Control Point ◽  
Surface Protein ◽  
New Drugs ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Critical Question ◽  
Accelerated Approval ◽  
New Biomarkers

For a long time, chemotherapy remained the main treatment option for metastatic urothelial carcinoma (mUC). Over the past year, there have been revolutionary changes associated with the approval of five new drugs aimed at blocking the interaction between the surface protein of T‑lymphocytes PD‑1 and its ligands PD‑L1 and PD‑L2, resulting in the activation of the immune response. It is noteworthy that the anti‑PD‑1 antibody pembrolizumab demonstrated an increase in overall survival relative to chemotherapy in a randomized phase III trial in the second line with mUC. Based on this level 1 evidence pembrolizumab was approved by the US Food and Drug Administration (FDA). Nivolumab (antibody PD‑1) also demonstrated an increase in overall survival compared to historical control and was approved by FDA. Likewise, antibodies targeting PD‑L1, including atezolizumab, durvalumab and avelumab, received accelerated approval from the FDA as the second line of treatment for mUC. Some of these agents are approved in the first line by the results of phase II study (atezolizumab and pembolizumab received accelerated approval for first‑line treatment in patients not receiving cisplatin). Despite these many endorsements, clinical development of new biomarkers for selection of patients, who can get maximum advantages of immunotherapy and also for development the optimal therapy sequencing still are biggest and critical question for future investigation.The clinical introduction of biomarkers to determine optimal treatment of patients remains extremely important.

Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16036-e16036
Author(s):  
Jerome Fayette ◽  
Valentine Polivka ◽  
Sylvie Chabaud ◽  
Bertrand Favier ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Studies ◽  
Line Chemotherapy

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.

Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial

2014 ◽  
Vol 32 (23) ◽  
pp. 2423-2429 ◽  
Author(s):  
Helmut Oettle ◽  
Hanno Riess ◽  
Jens M. Stieler ◽  
Gerhard Heil ◽  
Ingo Schwaner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Folinic Acid ◽  
Karnofsky Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Gemcitabine Refractory

Purpose To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid–modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy. Patients and Methods A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status. Results Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001). Conclusion Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.

scholarly journals Role of immunotherapy in the management of hepatocellular carcinoma: current standards and future directions

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
A. Weinmann ◽  
P.R. Galle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Statistical Significance ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Promising Therapeutic Approach

 The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (hcc) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (fda) and the European Medicines Agency. In phase ii studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval by the fda of nivolumab and pembrolizumab for second-line treatment. However, phase iii trials of nivolumab in the first line and pembrolizumab in the second line as single agents failed to reach statistical significance, although clinical benefit for a subset of patients with long durations of response could be demonstrated. Despite that setback, immunotherapy for hcc is a promising therapeutic approach, and the combination of immunotherapy with other treatment modal­ities such as monoclonal antibodies, tyrosine kinase inhibitors, or local therapies has the potential to increase the overall response rate and survival. Recently, the results of a phase iii trial of combination atezolizumab–bevacizumab compared with sorafenib showed a highly significant survival benefit and median overall survival that was not reached in the immunotherapy arm, making the combination the preferred standard of care in first-line therapy. Despite the impressive results and generally good toxicity profile of immunotherapy, patients who respond to therapy constitute only a subset of the overall population, and response rates are still limited. This review focuses on the currently reported results and ongoing clinical trials of checkpoint inhibitor–based immunotherapy in hcc.

A population-based study evaluating metastatic renal cell cancer (mRCC) patients treated with interferon (IFN) alone, first-line IFN then second-line sunitinib, or sunitinib alone

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15572-15572 ◽  
Author(s):  
C. K. Kollmannsberger ◽  
D. Y. Heng ◽  
N. Murray ◽  
K. N. Chi
Keyword(s):  
Overall Survival ◽  
Standard Treatment ◽  
Population Based ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact

15572 Background: Previously, immunotherapy agents such as IFN were the only treatments available for mRCC. Sunitinib has demonstrated prolonged progression free survival in a phase III trial but overall survival benefit has yet to be determined and few patients (pts) with poor MSKCC prognostic profiles were included. Methods: The province-wide BC Cancer Agency Registry was cross-referenced to the central pharmacy database to identify all pts with the diagnosis of mRCC who were treated with IFN and/or sunitinib. Sunitinib became available after October 2005 under an expanded access program or as standard treatment. Three groups of pts were identified: Group A consisted of pts who received IFN alone between January 2003 to October 2005, Group B was all pts who progressed on first-line IFN after October 2005 and subsequently were treated with second-line sunitinib and Group C was all pts treated with first-line sunitinib. Baseline characteristics and overall survival were collected on all patients. Results: A total of 75 patients were identified with 36 patients in Group A, 23 patients in Group B, and 16 patients in Group C. Data are reported from the initiation of IFN in Group A and the initiation of sunitinib in Groups B and C. Median follow-up was 6.0 months in group A, 7.6 months in group B, and 6.2 months in group C. Median age of treatment initiation (62y vs. 60y vs. 62y), number of metastatic sites (>1 site in 63% vs. 61% vs. 56%), and Karnofsky performance status (79 vs. 86 vs. 81) were similar between groups A, B and C, respectively. The MSKCC prognostic profiles were favorable, intermediate and poor in 26%, 51% and 23% in group A, 17%, 65% and 17% in group B and 31%, 38% and 31% in group C, respectively. The estimated 6-month overall survival in groups A, B and C was 56%, 72% and 100%, respectively (log rank A vs C p=0.009; log rank B vs C p=0.042). Conclusion: With the limitations of retrospective analysis and preliminary follow-up, the introduction of sunitinib as standard treatment into the general population of patients with mRCC appears to be associated with a longer overall survival compared to patients treated with IFN alone. Population-based analysis on the impact of the introduction of sunitinib therapy is ongoing. No significant financial relationships to disclose.

Paclitaxel in relapsed squamous cell carcinoma of head and neck (SSCHN): Retrospective study of a single institution

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17047-e17047
Author(s):  
J. Fayette ◽  
A. Montella ◽  
T. Bachelot ◽  
P. Pommier ◽  
D. Girodet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Phase Iii ◽  
Second Line ◽  
Single Institution ◽  
First Line ◽  
Line P

e17047 Background: For relapse or metastatic SCCHN the standard treatment is the combination of cisplatin and 5FU that showed higher response rate than methotrexate but similar overall survival. Cetuximab demonstrated in a phase III (N Engl J Med. 2008;359:1116) its efficacy and paclitaxel showed efficacy in a phase II study (Cancer. 1998;82:2270). The objective of this study was to evaluate paclitaxel (P) in our institution in various situations. Methods: We retrospectively reviewed 56 pts with relapse or metastatic SSCHN treated with P in a single institution in Lyon (France) between June 2002 and February 2008. P was administered in first line for locally advanced disease, in first line for relapsed or metastatic disease, or in second or more line. P was administered q1w or q3w, alone or in combination with carboplatin or cetuximab. Results: Median age was 59 years (36–84) at the beginning of paclitaxel. Localizations of primitive tumor: oral cavity (14%), oropharynx (30%), hypopharynx (39%) larynx (7%), rhinopharynx (4%), or other (6%). All patients received adequate initial treatment with surgery and/or radiotherapy, 47% had have neoadjuvant chemotherapy (71% with cddp-5fu, but 5 pts received P). Five patients received P as neoadjuvant treatment. Among 52 evaluable patients, 33 received P in first line of treatment after relapse, 12 in second line. Monotherapy was administered to 20 patients and 22 received P combined with carboplatin, and 1 with cetuximab. For all patients, objective response rate (OR) was 30.8% (95% CI 18.7–45.1%). In first line of relapse, OR was 39.4% (95% CI 22.9–57.9%) and 16.7% (95% CI 2.1–18.4%) in second line. In monotherapy OR was 30.0% (95% CI 11.9–54.3%) and 36.4% (95% CI 17.2–59.3%) in combination with carboplatin. The overall survival (OS) of all patients was 6.3 months (95% CI 3.9–7.9 m), and 7.7 m (95% CI 3.9–11 m) and 5.2 m (95% CI 2.8–7.9 m) in first and second line, respectively. There is no difference in OS between monotherapy and combination: 6.1 m (95% CI 3.9–7.9 m) and 5.3 m (95% CI 3.9–7.9 m), respectively. Conclusions: P did not improve overall survival but showed interesting response rate in relapsed patients who are often symptomatic. Recent studies suggest high potentialities in combination with EGFR inhibitors. No significant financial relationships to disclose.

Prostate-specific antigen decline (PSA) as a surrogate for overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) who failed first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4515-4515 ◽  
Author(s):  
Susan Halabi ◽  
Andrew J. Armstrong ◽  
A. Oliver Sartor ◽  
Johann Sebastian De Bono ◽  
Ellen B Kaplan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Specific Antigen ◽  
Phase Iii ◽  
Surrogate Endpoints ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Psa Kinetics ◽  
Psa Velocity ◽  
Line Chemotherapy

4515 Background: PSA kinetics, and more specifically a 30% decline in PSA following initiation of first-line chemotherapy with docetaxel, has been reported to be a surrogate endpoint for OS in mCRPC pts. The objective of this analysis was to evaluate PSA kinetics as surrogate endpoints for overall survival (OS) in patients who were receiving second line chemotherapy following progression after docetaxel front line therapy. Methods: Data from a phase III trial of 755 mCRPC pts randomized to treatment with cabazitaxel in combination with prednisone (C+P) every 3 weeks or mitoxantrone in combination with prednisone (M+P) were used. All pts were previously treated with a docetaxel-containing regimen. PSA decline (≥30% and ≥50% ) and PSA velocity within the first three months of treatment were evaluated as potential surrogate endpoints for OS. The proportional hazards (PH) model was used to test for Prentice’s criteria and the proportion of treatment explained (PTE) was computed as a second test of surrogacy. PTE was defined as one minus the ratio of the treatment coefficient in the adjusted PH model (includes PSA decline or velocity) to the treatment coefficient in the unadjusted PH model. Results: Of 755 men, 654 had sufficient PSA data to be included in the analysis. Treatment arm (C+P vs. M+P) was prognostic of OS with a hazard ratio (HR) of 0.65 (95% CI=0.54-0.79, p<0.001). A 30% PSA decline within three months of treatment was associated with a HR of 0.46 (95% CI 0.37-0.57, p-value<0.001) for OS. After adjusting for treatment effect, the HR for 30% PSA decline was 0.50 (95% CI= 0.40-0.62, p<0.001) but treatment arm remained statistically significant thus failing Prentice’s third criterion. The PTE for ≥30% decline in PSA within three months was 0.39 (95% CI= 0.36-0.42) indicating a lack of surrogacy for OS. Similar results were observed for pts who experienced ≥50% decline in PSA and PSA velocity. Conclusions: Neither PSA decline (≥30% and ≥50%) nor PSA velocity within the first three months of therapy are surrogate endpoints for OS in pts receiving second line chemotherapy.

Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15007-e15007
Author(s):  
Ronan Fougeray ◽  
Toni K. Choueiri ◽  
Francesc Pons ◽  
Fabio Augusto Barros Schutz ◽  
Yacine Salhi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Supportive Care ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Line Setting

e15007 Background: Standard first-line therapy of advanced TCCU is based on cisplatin-based combinations. In patients deemed unfit to receive CISPLATIN, carboplatin-based or non-platinum combinations are considered. A phase III trial comparing vinflunine (VFL) and best supportive care (BSC) with BSC alone for second-line treatment of advanced TCCU patients demonstrated a survival advantage for VFL+BSC. We studied the impact of the first-line platinum therapy on overall survival in second line setting. Methods: Eligible 357 patients of the phase III study were split in the two following subsets: CISPLATIN (Patients with prior CISPLATIN administration) and NO CISPLATIN (patients without prior CISPLATIN administration). Survival was measured from the date of random assignment. Overall Survival (OS) was calculated using Kaplan-Meier method, with log-rank comparisons. Multivariate Analysis of OS was analyzed with the Cox proportional hazards model, including prognostic factors for second-line setting previously identified (Bellmunt, 2010). Updated survival data in 11/2008 cut-off date was used. Results: CISPLATIN group represented 70.3% (n=251) and NO CISPLATIN 29,7% (n= 106). CISPLATIN group had less Liver involvement (25% vs 43%, p=0.0007) and better WHO-PS (>1: 66% vs 76%; p=0.0478). OS was higher in CISPLATIN group for all eligible patients (HR: 0.77; CI 95% 0.61-0.97; p=0.0294), for VFL+BSC arm (HR: 0.78; CI 95% 0.59-1.02; p=0.0693) and for BSC arm (HR: 0.68; CI 95% 0.42-1.08; p=0.0978). Multivariate analysis including prognostic factors (liver involvement, hemoglobin, PS) and prior platinum administration, did not show effect of CDDP on OS. VFL reduced the risk of death by 24% in CDDP-group (HR: 0.76; CI 95% 0.58-0.99; p=0.043) and by 35% in NO CDDP –group (HR: 0.65; CI 95% 0.41-1.04; p=0.0724). Conclusions: Differences in prognostic factors between CISPLATIN and NO CISPLATIN groups may explain the differences in OS in patients who undergo 2nd line therapy. The choice of Cisplatin or no Cisplatin chemotherapy in the first line did not impact subsequent benefit of vinflunine over best supportive care.

scholarly journals Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 640-662
Author(s):  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
New Drugs ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Recent Advances

Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib increased the available treatment options for patients with extrahepatic spread and vascular invasion and improved survival in patients with advanced HCC; however, various shortcomings such as low response rates and relatively high toxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at developing new molecular targeted agents to provide more treatment options and second-line agents for patients with disease progression or intolerance to sorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all first-line and second-line clinical trials conducted during this period failed. However, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. In addition, nivolumab and pembrolizumab were approved as second-line agents after sorafenib. A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review describes the recent advances in systemic therapy and the use of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal antibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the similarity of their efficacy and safety profiles to those in the general population.

scholarly journals Targeting EGFR in Esophagogastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Steven B. Maron ◽  
James Xu ◽  
Yelena Y. Janjigian
Keyword(s):  
Overall Survival ◽  
Clinical Benefit ◽  
Routine Care ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Metastatic Setting ◽  
Esophagogastric Cancer ◽  
Phase Iii Trials ◽  
Related Mortality

Esophagogastric cancer (EGC) remains a major cause of cancer-related mortality. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to-date: only first line anti-HER2 therapy in ERBB2-expressing tumors, second line anti-VEGFR2 therapy with ramucirumab in unselected patients, and pembrolizumab in PD-L1 expressing or MSI-H patients. EGFR inhibitors were extensively studied in EGC, including phase III trials with cetuximab (EXPAND), panitumumab (REAL3), and gefitinib (COG). All three trials were conducted in unselected populations, and therefore, failed to demonstrate clinical benefit. Here, we review previous attempts at targeting EGFR in EGC and potential future biomarkers for targeting this pathway in patients with EGFR-amplified tumors.

Best supportive care in combination with polychemotherapy versus best supportive care alone as second-line therapy in stage IV metastatic melanoma (DeCOG MM-PAL 8)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8567-8567
Author(s):  
J. Ulrich ◽  
U. Trefzer ◽  
W. Tilgen ◽  
D. Schadendorf ◽  
M. Kaatz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Supportive Care ◽  
Metastatic Melanoma ◽  
Stage Iv ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

8567 Background: To date, there is no evidence of survival benefit from randomized trials in stage IV metastatic melanoma (MM) after disease progression to first-line therapy. Therefore, we initiated a phase III trial to evaluate the impact on survival of polychemotherapy in patients (pts.) receiving best supportive care (BSC) as second-line therapy. Methods: This prospective multicenter controlled study was conducted by the Dermatologic Cooperative Oncology Group (DeCOG) with 13 participating centers. Pts. with stage IV MM disease between 18 and 75 yrs. and a Karnofsky performance status (KPS) > 60 with progression after first-line chemotherapy or chemo-immunotherapy were offered to choose between polychemotherapy + BSC or BSC alone. Pts. were required to have adequate renal, liver and bone marrow function. The regimen consisted of cisplatin (50 mg/m2), vindesine (3 mg/m2) and dacarbacin (450 mg/m2) given on day 1 and 8 every 28 days (CVD). Reevaluation according to WHO response criteria were performed every 2 cycles. Primary endpoint was the median overall survival (OS). Secondary endpoints were overall response rate (OR) (only CVD arm) and quality of life (QOL). Results: Between 1/02 and 8/06 120 pts. were recruited, a minority of 35 pts. (29%) chose the BSC arm (A) and 85 (71%) the CVD + BSC arm (B). Five pts. were ineligible, and thus 115 pts. treated per protocol. There was a significant lower KPS in arm A at study entry. At the time of data analysis, 85% of the pts. had died from melanoma. There was no siginificant difference (p=0.093) in median OS between the two arms, 9.0 [95% CI: 3,9–14,1] months in arm A and 8.0 [95% CI: 6,5–9,5] months in arm B. The OR in arm B was 7.5% (2 CR, 3 PR). Conclusions: Polychemotherapy (CVD) + BSC as second-line therapy in stage IV MM does not improve overall survival as compared to BSC alone. No significant financial relationships to disclose.

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