Pathological complete response induced by first-line chemotherapy with single agent docetaxel in a patient with advanced non small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Defining the optimal treatment for patients with inoperable non small cell lung cancer (NSCLC), presenting with metastatic mediastinal lymph nodes, is challenging. Nevertheless, preoperative chemotherapy or radiotherapy might offer a chance for these patients for radical surgical resection and, possibly, complete recovery.</p> <p>Case Presentation</p> <p>A 62-year old man with IIIA-N2 inoperable NSCLC was treated with first-line single agent docetaxel. A platinum-based treatment, though considered more active, was ruled out because of renal impairment. The patient tolerated the treatment very well and, although his initial response was not impressive, after 14 cycles he obtained a complete clinical response, which was confirmed pathologically after he underwent surgical lobectomy.</p> <p>Conclusion</p> <p>In non-operable NSCLC patients not eligible for a platinum-based treatment, single-agent docetaxel can provide complete pathologic responses. Failure to obtain a response after the first few cycles should not automatically discourage to continue treatment.</p

Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

Abstract Background: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as diseaserelated survival improves. There are few data on the natural history of bone disease in RCC

Economic evaluation of temsirolimus on the basis of the results of the ARCC (Advanced Renal-Cell Carcinoma) study

Introduction: metastatic renal cell carcinoma (mRCC) is highly resistant to chemotherapeutics, rendering limited antitumor effect. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. The Global ARCC Trial (Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma) compared temsirolimus alone or temsirolimus plus interferon alfa with interferon alfa alone in mRCC. It has demonstrated that, as compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis while the addition of temsirolimus to interferon did not improve survival. Aim: the objective of our study was to investigate the pharmacoeconomic impact in the Italian context of temsirolimus vs interferon alfa in patients with metastatic renal-cell carcinoma and a poor prognosis. Methods: economic evaluation is based on clinical outcome data from the ARCC trial and was carried out conducting a cost/effectiveness analysis, comparing economic and clinical consequences of temsirolimus (25 mg weekly) vs interferon alfa (18 MU 3 times weekly) in the perspective of the Italian National Health Service. Direct medical costs included in the analysis were drug costs, costs associated with the management of treatment-related serious adverse events (grade 3 and 4), cost related to progression and best supportive care. Effects were measured in terms of overall survival. A sensitivity analysis was performed. Results: the cost of temsirolimus or interferon alfa therapy amounted to approximately € 14,000 and € 2,000 patient respectively. The cost of hospitalization related to drug toxicity was about € 1,500 for temsirolimus and € 2,100 for interferon alfa. Temsirolimus shows an incremental cost per patient per month saved of € 3,767. Sensitivity analysis demonstrates that cost consequences parameters are sensitive to fluctuation. Discussion: this study is the first economic evaluation of ARCC trial based on the Italian context. This evaluation found that temsirolimus therapy in patients with metastatic renal-cell carcinoma and a poor prognosis is cost-effective

Preliminary safety results of an Italian early-access program (EAP) with cabazitaxel plus prednisone (CbzP) in patients with docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC)

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of &gt; 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. Methods: We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m2 Q3W) plus P(10mg bid). Results: Pts were median age 73.5 years (&gt;75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D dose to inclusion was 7.1 months. Overall, 62.5% (10 Pts) had 2 or more metastatic sites (bone 94%, regional/distant lymph nodes 25% and 44%, lung 12.5%, other sites 19%). A limited number of relevant adverse events (AE) were observed. All grade AEs were seen in 14/16 pts (81.3%), with 4/16 pts experiencing grade 3/4 leukopenia, 8/16 pts grade 3 - 4 neutropenia, one patient with febrile neutropenia and one with hypertransaminasaemia. Grade 1-2 asthenia and fatigue were experienced respectively by 2 pts. No grade 3 / 4 diarrhea, vomiting or constipation were observed and no AEs results in death. All pts received at least 2 cycles of CbzP (2÷5) and only one patient permanently discontinued treatment (disease progression). Conclusions: This preliminary analysis of Italian pts enrolled in the EAP provides real world safety data and suggests a good safety profile of cabazitaxel even in heavily pretreated pts, which is in agreement with Italian experience in TROPIC. Results of the entire Italian cohort with a longer follow-up will be presented. </jats:p

Which data for cabazitaxel (Cbz) from the real world? The safety experience from the Italian centres participating in the Expanded Access Programme (EAP)

189 Background: A significant percentage of metastatic castration-resistant prostate cancer (mCRPC) patients (pts) progressing during or after a docetaxel (D) based therapy are candidates for additional effective treatments. Taxanes remain the mainstay of treatment for a wide range of tumours including mCRPC. Cabazitaxel, a next generation of taxane, was approved based on results from the TROPIC study (NCT00417079). Cbz plus prednisone (P) was associated with a higher overall survival than mitoxantrone (MTX) (15.1 vs 12.7 mo, HR=0.70; P&lt;0.0001). Moreover CbzP was associated with clinical benefits, better PFS, maintenance of ECOG PS, improved tumour and PSA response, longer time to tumour and PSA progression while pain control was similar to MTX. These clear benefits supported a global EAP. Methods: Here we report, the preliminary safety analysis of 165 pts entered in the study from 25 Italian centres between Jan and Nov 2011. Pts received Cbz 25 mg/m2(intravenous every 3 weeks) plus P 10 mg (oral daily). Results: Median age was 70 years (21.8% of the cases were ≥75 years); pts with PS 0-1=98.2%; median number of previous D cycles was 8; 30.8% received 450 ÷ 675 mg, 14.7% received 675 ÷ 900 mg and 28.2% received ≥ 900 mg of D. Median time from last D dose to first CbzP dose was 5 months including any other eventual chemotherapy treatment. 49.1% of the pts entered in this EAP because refractory to D (PD during or within 3 months since the last D administration), overall 72 % of pts had 2 or more met sites. At the time of this analysis approximately 50% of pts received 4 cycles. A total of 68 pts discontinued CbzP due to PD (38.2%), AEs related and not related (38.2)%, Investigator’s decision (2.9%) or other reasons (20.6%). The most common G 3/4 AEs were neutropenia (35.2%), leukopenia (17.6%), anaemia (5.5%) febrile neutropenia (4.2%); main non-haematological AEs were asthenia (4.8%) and fatigue (4.2%). Conclusions: This large analysis confirms a manageable safety profile of cabazitaxel in routine clinical practice. The safety profile showed in EAP study suggests cabazitaxel a safe and effective treatment option in mCRPC pts progressing during or after a docetaxel based therapy. Clinical trial information: NCT01254279. </jats:p

First-line pazopanib in patients with advanced non-clear cell renal carcinoma: An Italian case series

BACKGROUNDNon-clear cell (ncc) metastatic renal-cell carcinoma (RCC) has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart. New systemic combination therapies have emerged for metastatic RCC (mRCC), but the pivotal phase III trials excluded patients with nccRCC, which constitute about 30% of metastatic RCC cases.AIMTo provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODSThe present study is a multicenter retrospective observational analysis aiming to assess the activity, efficacy, and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTSOverall, 48 patients were included. At the median follow-up of 40.6 mo, the objective response rate was 27.1%, the disease control rate was 83.3%, and the median progression-free survival and overall survival were 12.3 (95% confidence interval [CI]: 3.6-20.9) and 27.7 (95%CI: 18.2-37.1) mo, respectively. Grade 3 adverse events occurred in 20% of patients, and no grade 4 or 5 toxicities were found.CONCLUSIONPazopanib should be considered as a good first-line option for metastatic RCC with variant histology