Efficacy In Terms Of Response Research Articles

Management of Hepatocellular Carcinoma in Decompensated Cirrhotic Patients: A Comprehensive Overview

Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for 75% of primary liver cancer cases, mostly on the basis of cirrhosis. However, the data and therapeutic options for the treatment of HCC in patients with decompensated cirrhosis are rather limited. This patient category is often considered to be in a terminal stage without the possibility of a specific treatment except liver transplantation, which is restricted by several criteria and liver donor shortages. Systemic treatments may provide a solution for patients with Child Pugh class B or C since they are less invasive. Although most of the existing trials have excluded patients with decompensated cirrhosis, there are increasing data from real-life settings that show acceptable tolerability and satisfying efficacy in terms of response. The data on the administration of locoregional treatments in such patients are also limited, but the overall survival seems to be potentially prolonged when patients are carefully selected, and close adverse event monitoring is applied. The aim of this review is to analyze the existing data regarding the administration of treatments in decompensated patients with HCC, evaluate the effect of therapy on overall survival and highlight the potential risks in terms of tolerability.

Phase II trial of durvalumab plus tremelimumab with concurrent radiotherapy (RT) in patients (pts) with localized muscle invasive bladder cancer (MIBC) treated with a selective bladder preservation approach: IMMUNOPRESERVE-SOGUG trial.

4505 Background: Bladder-preserving combined-modality therapies constitute an alternative to radical cystectomy for selected pts with MIBC. In preclinical studies, combination of radiation and dual checkpoint blockade appears to activate non-redundant immune mechanisms, potentiating antitumor activity. The purpose of the present study is to explore feasibility, toxicity and activity of this approach in MIBC. Methods: Pts with localized MIBC in clinical stages T2-4a N0 M0, ECOG 0-1, without contraindications to immunotherapy, who either wished for bladder preservation or were ineligible for cystectomy, were included in this phase II study. Treatment consisted of initial transurethral resection (TUR) of the tumor, followed by durvalumab 1,500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for 3 doses. Normofractionated external-beam RT was started 2 weeks later, at doses of 46 Gy to minor pelvis and 64-66 Gy to bladder. Pts with either residual or relapsed MIBC were offered salvage cystectomy. The primary endpoint was complete response (CR) defined as absence of MIBC at post-treatment tumor site biopsy. A 2-stage sequential design was used (CR rate P0=5, P1=0.7, α=0.10, β=0.20) requiring at least 6 CR in the first 12 pts to expand to a second cohort of 20 pts. Results: From 1/2019 to 8/2020, 32 pts were enrolled at 6 centers. Median age was 71 years (49-91). PS was 0 in 24 pts,1 in 8. 25 were males. Clinical stage was T2 in 28 pts, T3 in 3 and T4a in 1. All pts received at least two immunotherapy cycles. The median dose of RT administered was 64 Gy (60-65). CR at post-treatment biopsy was documented in 26 (81%) pts, 2 pts had residual MIBC and 4 pts were not evaluated due to rejection (1), clinical impairment (1), death from COVID 19 (1) and a suspected treatment-related death from peritonitis (1). After a median follow up of 6.1 months (2.5 - 20.1), 2 pts underwent salvage cystectomy because of MIBC and T1 relapses, respectively. The estimated 6-months rates for disease-free survival (DFS) with bladder intact, DFS and overall survival were 76% (95%CI, 61%-95%), 80% (95%CI, 66%-98%) and 93% (95%CI, 85%-100%), respectively. A total of 31 (97%) pts experienced adverse events related to RT and/or immunotherapy, with diarrhea (41%) and urinary disorders (37.5%) as the most frequent. Grade 3 or 4 adverse events related to therapy were reported in 31% pts, being the most frequent gastrointestinal toxicity (12.5%), acute kidney failure (6%) and hepatitis (6%). Conclusions: A combined-modality approach including durvalumab + tremelimumab with concurrent RT is feasible and safe, showing high efficacy in terms of response and eliciting bladder preservation in a large number of pts. Further research on this approach as an alternative to cystectomy is warranted. Clinical trial information: NCT03702179.

Efficacy of amoxicillin-clavulanic acid versus ceftriaxone in children hospitalized under 5 years of age with uncomplicated community acquired pneumonia.

Objectives: Community acquired pneumonia (CAP) is considered to be the commonest reason for hospitalization among children. Pneumonia is the leading cause of mortality among children in Pakistan in children, causing 33% of all deaths in infants and 37% of all deaths in children 1 to 4 years. The aim of current study was to compare efficacy of amoxicillin-clavulanic acid versus ceftriaxone among children under 5 years of age, hospitalized having uncomplicated CAP. Study Design: Randomized Controlled trial (RCT). Setting: Department of Pediatric Medicine, The Children Hospital and Institute of Child Health, Lahore. Period: 01/01/2019 to 30/06/2019. Material & Methods: A total of 210 (105 in each group) children aged between 2 to 60 months, diagnosed having CAP were randomly allocated into either Group-A (received IV amoxicillin-clavulanic acid) or Group B (received IV ceftriaxone). Efficacy in terms of response of both treatment groups was noted after 5 days treatment. Results: Overall, mean age was noted as 14.68±15.7 months. Majority (n=131, 32.4%) were male and aged between 1 to 12 months (n=135, 64.3%). Mean duration of symptoms was noted as 3.60±1.69 days. Efficacy was significantly higher in children treated with ceftriaxone as compared to those treated with Amoxicillin/Clavulanic acid (96.2% vs. 76.2%; p<0.001). This difference was significant across all age, gender and duration of symptom groups (p<0.05). Conclusion: The efficacy was significantly higher in children treated with ceftriaxone as compared to Amoxicillin/Clavulanic acid.

Thymic malignancies: emerging systemic therapies.

The management of thymic malignancies is based on multidisciplinary collaboration. Systemic agents may be administered as an exclusive treatment if local treatment is not achievable. Novel and innovative agents are needed. Integrated genomic analyses reported the activation of targetable signaling pathways in thymomas and thymic carcinomas. Phase II trials reported the antitumor activity of phosphatidylinositol 3-kinase/mechanistic target of rapamycin kinase inhibitors, cyclin dependent kinase inhibitors, and antiangiogenic agents in advanced, refractory thymic malignancies. Meanwhile, a major challenge is the use of immune checkpoint inhibitors, given the frequent association of those tumors with autoimmune disorders. Although those innovative agents were assessed in phase II trials reporting on variable antitumor efficacy in terms of response and survival, in selected and limited cohorts of patients, a better understanding of systemic treatment sequences in a real-life setting is mandatory to analyze the actual efficacy of each line of treatment one after another, define the best clinical-pathological selection of patients for the administration of chemotherapy, targeted agents, and immunotherapy, and develop individualized decision-making to optimize the survival of patients with advanced thymic malignancies.

Application of time-dependent modeling for the exposure-efficacy analysis of ceritinib in untreated ALK-rearranged advanced NSCLC patients.

Ceritinib 750mg/day was approved for the treatment of patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) based on ASCEND-4 study. The objective of this article is to introduce the use of time-dependent modeling approach in the updated exposure-efficacy analysis of ceritinib for the first-line indication. Exposure-efficacy analyses, including data from 156 patients, were first conducted using time-independent logistic regression model for response of complete or partial response and Cox regression model for progression-free survival (PFS). The exposure measure used was average Ctrough, which is defined as the geometric mean of all evaluable Ctrough for each patient. To further investigate the impact of exposure measure on exposure-efficacy analyses, a time-dependent modeling approach was used, where exposure at different time intervals was associated with the corresponding response endpoints in a longitudinal manner. With exposure measure being average Ctrough, it was observed that higher exposure was associated with reduced efficacy in terms of response (odds ratio = 0.77) and PFS [hazard ratio (HR) = 1.12]. These time-independent models do not account for the impact of time-varying concentration due to dose modifications. Subsequently, a new time-dependent modeling approach was used, where exposure and efficacy were associated longitudinally in the analyses. The results showed that the odds ratio of response became 1.07, and the HR of PFS became 1.04, indicating no apparent reverse relationship between exposure and efficacy across the exposure range studied. The drug effect on efficacy in clinical trials could be better characterized using time-dependent exposure-response models.

A Comparative Study on Weekly Versus Three Weekly Cisplatinum Based Chemoradiation in Locally Advanced Head and Neck Cancers.

Head and Neck Cancers constitute around 30% of cancers occurring in India and majority of cases present with locoregionally advanced disease. Cisplatin based concurrent chemoradiation is the most common modality of definitive treatment in these advanced cases. However, it is unclear regarding priority of weekly versus three weekly cisplatin based concurrent chemoradiation schedule in treatment of such advanced diseases. To evaluate the efficacy in terms of response, locoregional control, and disease status in both the arms, and to compare the acute and late toxicity in both arms. Thirty untreated patients of locally advanced Squamous Cell Carcinoma of head and neck were randomized into two arms: Arm A (n=15) patients received injection cisplatin 30 mg/m2 weekly along with radiation; Arm B (n=15) patients received injection cisplatin 100 mg/m2 on a three weekly basis along with radiation. Radiotherapy was delivered to a total dose of 66 Gy in conventional fractionation schedule in telecobalt machine. Major toxicities included mucositis, dermatitis, vomiting, neutropenia, and anaemia. There was a trend towards increase in grade-III leukopenia and grade-III dermatitis in arm A compared to arm B, and increase in grade-III mucositis and grade-III vomiting in arm B in comparison to arm A although statistically not significant. Within a median follow-up of seven months, in arm A complete response was 73.33% (11/15) and partial response was 26.67%; whereas in arm B complete response was 85.71% (12/14) and partial response was 14.29%, which was not statistically significant. However, there was a trend towards better efficacy in arm B. We conclude that, weekly cisplatin arm is as good as three weekly cisplatin arms. But efficacy is not statistically significant. However, there was a trend of three weekly cisplatin arms towards better efficacy, with comparable haematological and mucosal toxicities.

Antidepressant augmentation: good news, limitations, and stumbling blocks.

Dr Zhou and colleagues have done an excellent job of reviewing and analyzing the world's literature on the efficacy and tolerability of pharmacologic agents used to augment antidepressants in treatment-resistant unipolar major depression. It seems we have some good news, but a lot remains to be accomplished. The good news is that several agents were found to have significant efficacy in terms of response (4 agents) and remission (6 agents) in comparison to placebo.

High Response Rates to Bortezomib-Dexamethasone Followed by Donor Lymphocyte Infusions in Patients with Multiple Myeloma Relapsing After Allogeneic Stem Cell Transplantation: Results of a Multicentric Prospective Phase II Study

Abstract 828 Introduction:Patients with multiple myeloma (MM) relapsing or progressing after allogeneic stem cell transplantation (alloSCT) have limited therapeutic options. Donor lymphocyte infusions (DLI) are used to exploit the graft-versus-myeloma effect, and pilot studies have shown that cytoreduction before DLIs could increase their efficacy. These patients are often chemo-refractory or frail, so the new drugs are an attractive option in this setting. Based on experimental and pilot studies showing the high efficacy of bortezomib in alloSCT relapse of MM, we designed a prospective multicenter study to treat these patients with 3 cycles of bortezomib-dexamethasone (VD) followed by escalating doses of DLIs (VD-DLI). The primary objective was the efficacy in terms of response as defined by IMWG criteria. Secondary objectives were to assess the incidence of GVHD, the incidence of graft failure, the progression free survival (PFS), the overall survival (OS), and the safety. Methods:Patients with relapsing or progressive MM after alloSCT were enrolled. Treatment consisted of three 21-day cycles with bortezomib 1.3mg/sqm/day iv at days 1, 4, 8, 11, and oral dexamethasone 20mg/day at days 1–2, 4–5, 8–9, 11–12, followed by 4 DLIs at escalating cell doses administered every 6 weeks. The DLIs started from 5×10^6 CD3+/kg cell dose for HLA-identical sibling donors, or 5×10^5 CD3+/kg for mismatched siblings, matched unrelated (MUD), or haploidentical donors. For every patient, the cell dose was escalated by 0.5 Log at each DLI until a maximum of 1×10^8 CD3+/kg and 1×10^7 CD3+/kg dose at the fourth DLI for HLA identical and alternative donors, respectively. DLIs were stopped anytime in case of acute GVHD, or if patients achieved >=CR after at least 2 DLIs. A safety interim analysis was run after the enrollment of the first 10 patients. Here we presented the final analysis of the study. Results:Nineteen patients were enrolled at 4 Italian transplant centers between 2007 and 2010. Sixteen patients had ISS stage I MM, two had ISS stage II, and one had ISS stage III MM. FISH data were not available. Median patients’ age was 58 years (range, 34–68 years), 8 patients were female. Patients had been treated with a median of 2 lines of therapy (range, 2–5 lines): all the patients had received at least one autologous transplant, 10 had received thalidomide, 4 patients had received bortezomib and none of them was bortezomib-refractory. Two patients had grade (G) 1 peripheral neuropathy (PN) owing to previous treatments. Fifteen alloSCT donors were HLA identical siblings, 3 were MUD and one was haploidentical. One patient received one VD, one 2 VD, and 17 patients all the 3 planned VD. Two patients received one DLI, 1 patient 2 DLIs, 6 patients 3 DLIs, and 8 patients 4 DLIs. The median follow-up of the 15 (79%) surviving patients is 22 months (range, 12.5–55 months). Overall response rate (ORR) to VD was 63%: 3 patients achieved PR, 7 patients VGPR, 1 patient CR and 1 sCR; patients with SD were 5. The 17 patients receiving VD and DLIs had a 71% ORR, with 1 patient achieving PR, 7 patients achieving VGPR, 2 patients CR and 2 sCR; disease was stable in 4 patients. Twelve patients (63%) eventually progressed at a median time of 8.7 months (range, 1–22 months). Progression-free survival was 47% at one year and 33% at both 2 and 3 years of follow-up (median PFS, 12 months). Overall survival was 90% at 1 year and 79% at both 2 and 3 years of follow-up (median not reached). The incidence of aGVHD was 18% (3 patients: 2 had grade 1 and one grade 2). Five patients (29%) had limited cGVHD, none had extensive cGVHD. None of the patients experienced graft failure. During VD, 2 patients experienced G2 hematologic toxicity (thrombocytopenia). PN occurred in 5 patients (26%): 4 patients had G2 PN, and one patient had G3 PN. Other extra-hematologic toxicities more than G2 occurred only in one patient (G3 infection event). During DLI there were no >G2 hematologic or extra-hematologic toxicities. There were no treatment-related mortalities. Conclusion:This prospective study shows that VD-DLIs is feasible, well tolerated, and it can offer a high remission rate to patients with MM relapsed or refractory after alloSCT. Interestingly, the PFS and OS curves show a plateau, suggesting the achievement of a response more prolonged respect to the series previously published, relative to the non allotransplant setting. [protocol EudraCT number: 2006-004815-24]. Supported by Janssen-Cilag. Disclosures:Off Label Use: Bortezomib and Thalidomide as post autotransplantation consolidation therapy in myeloma.

Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution

Trabectedin was recently approved for patients failing doxorubicin, the standard treatment for advanced/metastatic sarcoma. This retrospective study aimed to compare trabectedin efficacy between compassionate use in unselected patients and clinical trials. From May 1999 to January 2006, 92 patients were treated at the Centre Léon Bérard, either in phase II studies or on a named patient compassionate basis. All cases were retrospectively analyzed to assess trabectedin efficacy in terms of response, progression-free, and overall survival.The objective response rate was 10% (N=9): 4% (N=2) for patients treated in compassionate use program and 16% (N=7) for those in clinical trials (P=0.18); 26 (28%) patients had stable disease for at least 6 months, 11 (23%) in the compassionate group and 15 (33%) in clinical trials. Median progression-free and overall survivals were, respectively, 2.2 [95% confidence interval (CI): 1.9-3.6] and 8.9 (95% CI: 6.4-14.2) months for all patients, 2.3 (95% CI: 1.9-4.3) and 10.4 (95% CI: 6.9-24.2) months for patients in clinical trials and 1.8 (95% CI: 1.4-3.4) and 6.4 (95% CI: 3.3-14.2) months for patients under compassionate treatment. In this retrospective analysis, the reported grade 3-4 toxicities were increased transaminase (34 patients, 37%) and neutropenia (38 patients; 42%). Higher efficacy was observed in phase II studies than with compassionate treatment, but no significant difference remained after adjustment in multivariate analysis for performance status, a well-established prognosis factor. The safety and tolerability of trabectedin shown in clinical trials is confirmed for patients in real-life situation treated in compassionate use programs, but its benefit is higher for patients with performance status 0-1.

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer

Background: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL).Methods: Patients were randomly assigned to receive cisplatin 80mg/m2 with NVBiv 30mg/m2 on day 1 and NVBo 80mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25mg/m2 on day 1 and NVBo 60mg/m2 on day 8 (arm A) or cisplatin 75mg/m2 and DCT 75mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms.Results: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0–4.2), 4.1 (3.4–4.5) (P=0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4–5.9), 5.1 (4.3–6.1) (P=0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4–11.6), 9.8 (8.8–11.5) (P=0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3–4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms.Conclusions: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.

Rituximab Plus Hypercvad Alternating with High Dose Methotrexate and Cytarabine for Patients with Newly Diagnosed Mantle Cell Lymphoma. A Multicenter Trial from GISL

BACKGROUND. Rituximab plus HyperCVAD alternating with High Dose Methotrexate and Cytarabine (R-HCVAD) has been tested in patients with newly diagnosed Mantle Cell Lymphoma (MCL) with promising results (Romaguera et al. JCO 2005). In 2005 the Gruppo Italiano Studio Linfomi (GISL) started a phase II multicenter study investigating clinical activity and toxicity of R-HCVAD in a similar group of patients.PATIENTS AND METHODS. To be included in the trial patients must have histologically confirmed diagnosis of MCL, be younger than 70 years, have adequate organ function. Chemotherapy consisted of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicine, and dexamethasone(considered one cycle) alternating every 21 days with rituximab plus high dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Patients with baseline PCR positivity for t(11;14) on bone marrow (BM) had to perform PCR assessment of BM at evaluation of response and during follow-up. Only patients achieving partial response (PR) were to be addressed to HDC followed by ASCT.RESULTS. Thirty-two patients were enrolled. There were 23 males and 9 females; median age was 54 yrs (29 to 66), 80% were in stage IV, 50% and 71% had Gastrointestinal (GI) and BM involvement, respectively; PCR for t(11;14) was positive on BM in 51% of cases. Seven patients did not complete treatment due to toxicity; of these, two patients died (one with septic shock at cycle 1, one with pulmonary aspergillosis at cycle 4), one patient had thrombosis of central line extended to right atrium at cycle 1, one had grade IV skin reaction at cycle 3, one had a severe pneumonia at cycle 1, two had persistent grade IV hematological toxicity after cycle 1 and 5, respectively. All patients had grade III–IV hematological toxicity. Response was assessed in 17 patients with 16 CR and 1 PR. PCR for t(11;14) negativity on BM was achieved in 4/9 patients after cycle 4 and in 8/9 after cycle 8. After a median follow-up of 24 months 1 patient progressed at 6 months and 1 patient relapsed after 26 months of follow-up. Two-year Failure Free Survival (FFS) was 75% (IC95% 53 to 87) and 2 year Disease Free Survival was 93%(IC95% 59–99).CONCLUSIONS. Though longer follow-up is needed R-HCVAD regimen used in our multicenter setting confirmed high efficacy in terms of response (both clinical and molecular) and FFS. However the regimen was associated to a severe toxicity profile that caused treatment discontinuation in several patients and that may limit its use in the clinical setting.

A phase II trial of low dose administration of 5-fluorouracil and cisplatin in patients with advanced and recurrent gastric cancer.

The clinical efficacy of chemotherapy for patients with advanced gastric cancer has not been established. We investigated in a phase II study the combination chemotherapy of low dose 5-fluorouracil (5-FU) and cisplatin (low dose FP) to evaluate its clinical efficacy in terms of response, quality of life and survival in 43 gastric cancer patients including 29 advanced and 14 recurrent cases. The administration of 5-FU was done by continuous intravenous infusion for 28 consecutive days with a dose of 250 mg/m2, while the administration of cisplatin was done by 1-h intravenous drip-infusion for 5 consecutive days and 2-day intervals per week with a dose of 3.5 mg/m2, that was repeated for 4 weeks in one cycle. The response rate in advanced cases was 48.3%, evaluated in 14 cases of partial response (PR), whereas its response rate in recurrent cases was 35.7%, evaluated in 5 cases of PR. The most effective lesions for low dose FP chemotherapy were primary lesion and lymph node metastasis. The quality of life assessed by performance status and oral intake was improved in 13.8% and 37.9% of advanced cases, and 21.4% and 28.6% of recurrent cases, respectively, as compared to those of pretreatment. The median survival time and 1-year survival rate were 6 months, 21.6% in advanced cases and 10 months, 28.8% in recurrent cases, respectively. The major adverse effect was observed in gastrointestinal toxicity and leukopenia, and the all toxicities were less than grade 2, that were controllable during the treatment. These results indicated that the combination chemotherapy of low dose administration of 5-FU and cisplatin might have therapeutic efficacy in tumor response and offer improvement in quality of life in patients with advanced and recurrent gastric cancer.

Combination chemotherapy with low doses of weekly Carboplatin and oral Etoposide in poor risk small cell lung cancer

Sixty patients with poor prognostic features, either with extensive disease (ED) or limited disease (LD) small cell lung cancer (SCLC), were treated on an out-patient basis with Carboplatin 80 mg/m 2 weekly for 3 weeks and oral Etoposide, at a dose of 100 mg, every other day for 21 days. The treatment was repeated every 5 weeks. Responding patients with LD were also treated with thoracic irradiation and those who achieved complete response (CR) received prophylactic cranial radio-therapy. The overall response rate (RR) was 32.1% with 8.9% CR. The responses were better for LD (RR 58.3%, CR 25%, partial response, PR 33.3%), than those for ED (RR 25%, CR 4.5%, PR 20.5%). The median time to progression (TTP) was 4.8 months and the median survival 5.5 months. These poor results could be attributed to the bad performance status and the presence of visceral and brain metastases in this group of patients. The results could also be due to the lower maximum concentration (C max) and higher T 1/2 of Etoposide, as measured in the blood and urine probably due to the modified regimen used in our study and to the organ insufficiency in this selected group of patients. Although, toxicity was generally mild and manageable, two toxic deaths occurred. In conclusion, this regimen appears to have a lower efficacy in terms of response and survival than that obtained in other studies using Cisplatin or Carboplatin plus Etoposide in a similar way. Therapy with this regimen, though less toxic, may not be a reliable alternative in elderly patients with visceral metastases and ECOG performance status ≥2.