Patterns of practice and pharmacoeconomic analysis of the management of patients with metastatic renal cell carcinoma (mRCC) in Greece--the CRISIS study. A retrospective analysis by the Hellenic Genitourinary Cancer Group (HGUCG).

Background:Metastatic RCC (mRCC) treatment has been revolutionized with 11 approved targeted agents. We report patterns of practice, outcomes and pharmacoeconomic analyses after the introduction of targeted therapy. Patients and methods: CRISIS was a retrospective multicenter study of mRCCpatients who received targeted therapy . Results were related to the start of 1st-line therapy, with a cut off at 1 January 2011 in order to depict the impact of increased availability of effective options. Results: 164 patients, were included. 70.1% and 44.5% received 2nd and 3rd-line therapy, respectively. More patients were treated in 2nd-line after 1 January 2011. After a median follow-up of 55.1 months, median progression-free (PFS) and overall survival (OS) were 10.7 (95% confidence intervals [CI]: 8.3-13.7), 7.3 (95% CI: 5.1-8.6), 5.8 (95% CI: 3.8-7.8) and 34 (95% CI: 28.5-39.8), 22.4 (95% CI: 16-32.1), 18.3 (95% CI: 12.4-26.4) months for first, second and third line, respectively. Efficacy of sunitinib and pazopanib in 1st-line were similar. The mean total cost/patient was 35,012.2 Euros (standard deviation [SD]: 28,971.5). Conclusions: Our study confirms previous real-world data suggesting that continuing advances in the treatment of mRCC produce favorable outcomes in everyday practice. Pharmacoeconomic analyses are important for cost-effective utilization of emerging novel therapies.

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 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.

Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group (HGUCG).

BACKGROUND: Advanced urothelial cancer (AUCa) is associated with poor long-term survival. Two major concerns are related to nonexposure to cisplatin-based chemotherapy and poor outcome after relapse. Our purpose was to record patterns of practice in AUCa in Greece, focusing on first-line treatment and management of relapsed disease. METHODS: Patients with AUCa treated from 2011 to 2013 were included in the analysis. Fitness for cisplatin was assessed by recently established criteria. RESULTS: Of 327 patients treated with first-line chemotherapy, 179 (55%) did not receive cisplatin. Criteria for unfitness for cisplatin were: Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2, 21%; creatinine clearance ≤ 60 mL/min, 55%; hearing impairment, 8%; neuropathy, 1%; and cardiac failure, 5%. Forty-six patients (27%) did not fulfill any criterion for unfitness for cisplatin. The main reasons for these deviations were comorbidities (28%) and advanced age (32%). Seventy-four (68%) of 109 patients who experienced a relapse received second-line chemotherapy. The most frequent reason for not offering second-line chemotherapy was poor PS or limited life expectancy (66%). CONCLUSION: In line with international data, approximately 50% of Greek patients with AUCa do not receive cisplatin-based chemotherapy, although 27% of them were suitable for such treatment. In addition, about one third of patients with relapse did not receive second-line chemotherapy because of poor PS or short life expectancy. Enforcing criteria for fitness for cisplatin and earlier diagnosis of relapse represent 2 targets for improvement in current treatment practice for AUCa.

Dedifferentiated paratesticular liposarcoma with osseous metaplasia.

Paratesticular liposarcoma is a rare tumour of the genitourinary track but the most common of all sarcomas in adults. The dedifferentiated variation occurs only in 10% of liposarcoma cases. The typical clinical presentation is similar to an inguinal hernia or a benign lipoma. We present the case of a dedifferentiated paratesticular liposarcoma with osseous metaplasia of the spermatic cord, in a male presented with acute scrotum.

Salvage treatment in metastatic breast cancer with weekly paclitaxel and bevacizumab.

BACKGROUND: Weekly paclitaxel (P) in combination with bevacizumab (B) is an effective regimen as initial treatment of metastatic breast cancer (MBC). We investigated in a phase II study the activity of the same regimen as salvage therapy in MBC. METHODS: Pretreated women with MBC received weekly P (90 mg/m(2) days 1, 8, 15) and B (10 mg/kg days 1, 15) every 28 days. B could continue after discontinuing P until disease progression. This was second-line chemotherapy for 30% and third-line or more for 70% of patients. RESULTS: A total of 40 patients were enrolled. Median age: 61 (range 32-80) years; postmenopausal: 80%; baseline ECOG performance status <2 in 80% of patients. Two patients (5%) achieved complete response, 10 (25%) partial response (overall response rate 30%; 95% CI 15.8-44.2), and 10 (25%) stable disease. The response rate was 28% for the patients who had previously received taxanes. After a median follow-up of 20.6 months, the median time to progression was 4.8 months (95% CI 1.7-7.8), median survival 13.0 months (95% CI 10.3-15.7), and the probability of 1-year survival 55.5%. Main grade 3-4 toxicities were neutropenia 42.5%, febrile neutropenia 5%, and asthenia 10%. There was one toxic death due to sepsis. CONCLUSION: The PB regimen is well tolerated and active as salvage therapy in pretreated women with MBC. It could be an effective option even for patients exposed to taxanes during prior treatments.

Second-line chemotherapy with capecitabine (Xeloda) and docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial.

PURPOSE: To investigate the efficacy and toxicity of the docetaxel and capecitabine combination in patients with previously treated, unresectable adenocarcinoma of the pancreas. PATIENTS AND METHODS: Patients with pancreatic adenocarcinoma, pre-treated with gemcitabine-based chemotherapy, were treated with capecitabine (800 mg/m(2) orally, twice a day for 14 days) and docetaxel (75 mg/m(2) i.v, on day 1), every 3 weeks. The primary end-point was overall response rate (RR). RESULTS: Thirty-one patients were enrolled in the study; 93.6% of them had a performance status (PS) of 0-1 and 96.8% had stage IV disease. Patients received a median of 4 cycles/patient, and the main reason for treatment discontinuation was disease progression. Partial response was observed in three (9.7%) patients, stable disease in seven (22.6%) (disease control rate: 32.3%, 95% CI: 15.80-48.71%) and disease progression in 21 (67.6%). The median progression-free survival (PFS) was 2.4 months (95% CI: 1.6-3.13) and the median overall survival (OS) was 6.3 months (95% CI: 3.38-9.23); the estimated 1-year survival rate was 14.7%. Grade III/IV neutropenia occurred in 10 (32.2%) patients and febrile neutropenia in one patient. Other severe non-hematologic toxicities were mild and manageable. After 2 chemotherapy cycles, pain control occurred in 20% of patients and stabilization of body weight in 40%. CONCLUSION: The combination of docetaxel/capecitabine may confer good disease control associated with improvement of quality of life as second-line chemotherapy in patients with metastatic pancreatic cancer.

A retrospective analysis of non-platinum-based first- and second-line chemotherapy in patients with advanced non-small cell lung cancer.

BACKGROUND: Platinum-based chemotherapy represents the standard of care for advanced non-small cell lung cancer (NSCLC) while non-platinum-based regimens are frequently administered in patients with relapse. A retrospective analysis of the sequence administration of these regimens in the first- and second-line setting was performed. PATIENTS AND METHODS: The records of patients enrolled in the Hellenic Oncology Research Groups's randomized advanced NSCLC trials from February 1997 to September 2006 were retrospectively reviewed. The efficacy of non-platinum-based chemotherapy administered as first- or second-line treatment (n=94, cohort A) was compared to that of non-platinum-based first-line followed by platinum-based second-line chemotherapy (n=267, cohort B), and the reverse sequence (n=123, cohort C). RESULTS: The objective response rate (ORR) to first-line chemotherapy was higher in cohort C compared to cohort A (45.5% vs. 25.5%, respectively, p=0.002) and cohort B (45.5% vs. 21.3%, p=0.0001). The ORR to second-line therapy was 17%, 13.1% (p=0.349) and 7.3% (p=0.027) in cohorts A, B and C, respectively. Time to progression and the overall survival were comparable among the three cohorts in both first- and second line therapy. CONCLUSION: Platinum-based first-line chemotherapy improved response rate compared to non-platinum-based regimens; however, the overall survival was comparable, irrespective of the sequence administration of these regimens is the first- and second-line setting.

A phase I trial of gemcitabine, docetaxel and carboplatin administered every 2 weeks as first line treatment in patients with advanced breast cancer.

OBJECTIVE: To determine the maximum tolerated doses (MTDs) and dose limiting toxicities (DLTs) of gemcitabine (GEM), docetaxel (DOC) and carboplatin (CARBO) combination. PATIENTS AND METHODS: A total of 33 previously untreated HER-2 negative patients with stage IIIB-IV breast cancer received escalated doses of GEM, DOC and CARBO all given sequentially on day 1 every 2 weeks. Twenty-three patients (70%) had previously received adjuvant or neoadjuvant chemotherapy. RESULTS: The recommended MTDs are GEM 1,500 mg/m(2), DOC 50 mg/m(2) and CARBO 3AUC. Seven dose levels were evaluated and neutropenia was the primary dose-limiting event. Of 319 chemotherapy cycles delivered, grade 3-4 neutropenia occurred in 13.5% of them with two cases of febrile neutropenia. Diarrhea and asthenia were the most common non-hematological toxicities. Three (16%) complete and 6 (32%) partial responses were observed among 19 patients with measurable disease. CONCLUSION: The biweekly administration of GEM, DOC and CARBO is a well-tolerated regimen which merits further evaluation.

A dose escalation study of the biweekly administration of paclitaxel, oxaliplatin and capecitabine in patients with advanced solid tumors.

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum-tolerated doses of the paclitaxel, oxaliplatin (LOHP) and capecitabine combination in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received escalating doses of paclitaxel (starting dose 100 mg/m2) and LOHP (starting dose 40 mg/m2) on days 1 and 15 and capecitabine (starting dose 800 mg/m2/day) on days 1-7 and 15-21 every 28 days. DLTs were evaluated in the first cycle. RESULTS: Sixteen patients were treated at four dose-escalating levels. Eleven (68.7%) patients had received two or more prior chemotherapy regimens. The DLT level was reached at paclitaxel 110 mg/m2, LOHP 50 mg/m2 and capecitabine 1,000 mg/m2/day. DLTs due to grade 2-3 neutropenia resulted in treatment delays. No febrile neutropenia or treatment-related death occurred. Grade 2-3 neutropenia occurred in 3 (19%) patients each, grade 2-4 fatigue affected 6 (37.5%) patients, and grade 2-3 neurotoxicity was observed in 2 (12.5%) and 1 (6%) patients, respectively. Two partial responses and four disease stabilizations were achieved. CONCLUSION: The recommended doses for phase II studies are paclitaxel 100 mg/m2 and LOHP 50 mg/m2 on days 1 and 15 and capecitabine 1,000 mg/m2/day on days 1-7 and 15-21 every 4 weeks. This regimen is well tolerated and merits further evaluation.