A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours

To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m−2, respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment. All but six (73%) patients had previously received at least one chemotherapy regimen. The DLT dose level was reached at PLD 12 mg m−2, PCX 110 mg m−2 and GEM 1000 mg m−2 with neutropaenia being the dose-limiting event. Of the 86 chemotherapy cycles delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are PLD 12 mg m−2, PCX 100 mg m−2 and GEM 1000 mg m−2 administered every 2 weeks. The PK data revealed no obvious drug interactions. Biweekly administration of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits further evaluation in various types of solid tumours

Real-world experience of everolimus as second-line treatment in metastatic renal cell cancer after failure of pazopanib

Aim: We aimed to provide real-life data on the outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus as second-line treatment after failure of first-line pazopanib. Patients and methods: Data from the medical charts of mRCC patients from 8 centers in Greece and Spain were ed. All patients had received or were continuing to receive second-line everolimus treatment after failure of first-line treatment with pazopanib. No other previous therapies were allowed. The primary end point was the determination of progression-free survival (PFS). Results: In total, 31 patients were enrolled. Of these, 26% had performance status (PS).0, 88% were of intermediate/poor Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, and only 61% had undergone prior nephrectomy. Median PFS was 3.48 months (95% CI: 2.37-5.06 months). Median overall survival (OS) from everolimus initiation was 8.9 months (95% CI: 6.47-13.14 months). Median OS from pazopanib initiation was 14.78 months (95% CI: 10.54-19.08 months). Furthermore, 32% of patients temporarily discontinued everolimus due to adverse events (AEs), and 22% of patients discontinued everolimus permanently due to toxicity. Most common toxicities were anemia (29%), stomatitis (26%), pneumonitis (19%), and fatigue (10%). Moreover, 14 AEs (27%) were graded as 3 or 4 and were reported by 13 patients (42%). Conclusion: This study provides data exclusively on the sequence pazopanib-everolimus in mRCC. Everolimus has a favorable safety profile and is active. The short PFS and OS could be attributed to the fact that the pazopanib-everolimus sequence was mainly offered to patients with adverse prognostic features, resulting in a modest increase in the combined OS of our population. © 2017 Koutsoukos et al

Real-world experience of everolimus as second-line treatment in metastatic renal cell cancer after failure of pazopanib

Konstantinos Koutsoukos,1,2 Aristotelis Bamias,1,2 Kimon Tzannis,1 Marta Espinosa Montaño,3 Vasiliki Bozionelou,4 Christos Christodoulou,5 Dimitra Stefanou,6 Haralabos Kalofonos,7 Ignacio Duran,3 Konstantinos Papazisis1,8 1Hellenic Genito-Urinary Cancer Group, 2Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece; 3Medical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 4Department of Medical Oncology, University Hospital of Heraklion, Heraklion, 52nd Oncology Clinic, Metropolitan Hospital, Piraeus, 61st Department of Medical Oncology, Saint Savvas Anticancer Hospital, Athens, 7Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, 8Euromedica General Clinic, Thessaloniki, Greece Aim: We aimed to provide real-life data on the outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus as second-line treatment after failure of first-line pazopanib.Patients and methods: Data from the medical charts of mRCC patients from 8 centers in Greece and Spain were reviewed. All patients had received or were continuing to receive second-line everolimus treatment after failure of first-line treatment with pazopanib. No other previous therapies were allowed. The primary end point was the determination of progression-free survival (PFS).Results: In total, 31 patients were enrolled. Of these, 26% had performance status (PS) >0, 88% were of intermediate/poor Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, and only 61% had undergone prior nephrectomy. Median PFS was 3.48 months (95% CI: 2.37–5.06 months). Median overall survival (OS) from everolimus initiation was 8.9 months (95% CI: 6.47–13.14 months). Median OS from pazopanib initiation was 14.78 months (95% CI: 10.54–19.08 months). Furthermore, 32% of patients temporarily discontinued everolimus due to adverse events (AEs), and 22% of patients discontinued everolimus permanently due to toxicity. Most common toxicities were anemia (29%), stomatitis (26%), pneumonitis (19%), and fatigue (10%). Moreover, 14 AEs (27%) were graded as 3 or 4 and were reported by 13 patients (42%).Conclusion: This study provides data exclusively on the sequence pazopanib–everolimus in mRCC. Everolimus has a favorable safety profile and is active. The short PFS and OS could be attributed to the fact that the pazopanib–everolimus sequence was mainly offered to patients with adverse prognostic features, resulting in a modest increase in the combined OS of our population. Keywords: pazopanib, everolimus, renal cell carcinom