Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6–12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data vs. predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment.Materials and methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS) and response rate (RR). OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models.Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI] = 16.6–39.7%) and median OS and PFS were 20 (95% CI = 20–21) and 12 (95% CI = 12, 16) weeks, respectively. Visceral metastasis (VM) and hemoglobin (Hb) ≤ 10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI) of 24 (20–40) weeks and 1-year (95% CI) OS of 13.7% (4.4–42.7%), while the 37 patients with 1 or 2 risk factors had median OS (95% CI) of 20 (16–20) weeks and 1-year (95% CI) OS of 6.7% (1.8–24.9%). Cetuximab-including regimens were associated with a trend for improved RR compared to other agents (Odds ratio = 5.05, 95% CI = 0.84–30.37, p = 0.077). Taxanes vs. non-taxane, and combination vs. single agent therapy was not associated with improved outcomes. The study is limited by its modest sample size.Conclusion: This is the first prognostic classification proposed for patients receiving salvage systemic therapy for advanced PSCC. The presence of VM and Hb ≤ 10 gm/dl was associated with poor OS and PFS. Cetuximab appeared to be associated with better RR. This prognostic model may assist in salvage therapy drug development for this orphan disease by improving interpretation of outcomes seen in nonrandomized data.
A single dose of palonosetron before the initiation of multiple oral doses of TMZ, in patients on treatment with steady doses of dexamethasone, provides a high protection against CINV throughout the overall phase (0-168 h). The pharmacological profile of palonosetron, compared to first-generation 5-HT3 receptor antagonists, may have an impact on its clinical efficacy.
Every-other-week maintenance cetuximab schedule was well tolerated and did not worsen toxicity that occurred during chemotherapy. In daily practice, this simplified schedule could improve compliance and possibly improve quality of life in patients with recurrent or metastatic HNSCC that showed no progression during first-line chemotherapy.
Until the recent approval of vinflunine, no standard second-line chemotherapy existed for advanced transitional cell carcinoma (TCC). Few data exist about third-line chemotherapy for metastatic disease. Although administered in up-front regimens, anthracyclines were never evaluated beyond second-line treatment. This study assessed the activity of pegylated liposomal doxorubicin (PLD) in patients with advanced TCC previously treated with two chemotherapy regimens. From May 2005 to June 2009, 23 patients with metastatic TCC were recruited: median age was 62 years (49-76 years) with a median ECOG PS of 1. Patients received PLD 35 mg/m(2) every 21 days. All patients were evaluable for efficacy and toxicity. No patient showed complete response. Three patients (13 %) had partial response; seven patients (30 %) showed stable disease for a disease control rate of 43 %. The median time to progression (TTP) was 4.1 months with a median survival time (MST) of 6.3 months. Treatment was well tolerated: no patient developed grade 4 toxicities. This is the first study which evaluated the role of anthracyclines as third-line chemotherapy in metastatic TCC. Despite its manageable profile of toxicity, PLD showed modest activity. Beyond second-line chemotherapy, supportive care still represents the best therapeutic option for patients with metastatic TCC.
Single-agent chemotherapy is the preferred treatment option in chemonaive elderly patients with advanced nonsmall-cell lung cancer (NSCLC). The role of combination chemotherapy in this setting is uncertain although several studies report satisfactory efficacy and safety using weekly paclitaxel and carboplatin (AUC=6) as first-line chemotherapy in elderly patients. It is still unclear which schedule of this regimen which could offer the best therapeutic index. The aim of this study was to evaluate the activity and tolerability of concomitant weekly administration of paclitaxel and carboplatin in untreated elderly patients with advanced NSCLC. From february 2005 to April 2008 36 consecutive elderly patients with advanced NSCLC were enrolled. Median age was 74 years (range, 70-83 years) and median ECOG PS was 1 (range, 0-1). patients received carboplatin (AUC=2) and paclitaxel 80 mg/m² on days 1,8 and 15 every 28 days. All patients were evaluable for efficacy and toxicity; a median of 4 cycles was administered. Twelve patients had partial response (33%; 95% C.I. 15,8-52,3%), 10 patients (28%) showed stable disease. The median time to progression (TTP) was 5.7 months (95% C.I. 3.1-8.6 months) with a median overall survival (MOS) of 9 months (95% C.I. 4.4-13.9 months). Toxicity was mild with no cases of febrile neutropenia; 5 patients (14%) developed grade 2 neuropathy. Our study confirms the substantial activity of weekly regimen of paclitaxel and carboplatin. Due to its favorable profile of toxicity this schedule could represent an interesting therapeutic option in selected chemonaive elderly patients with advanced NSCLC.
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