Classic list

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.

Polyzos A, Kalbakis K, Kentepozidis N, Giassas S, Kalykaki A, Vardakis N, Bozionelou V, Saloustros E, Kontopodis E, Georgoulias V, Mavroudis D.

Erratum in

• Oncology. 2006;71(3-4):203. Mavrousis, D [corrected to Mavroudis, D].

Abstract

PURPOSE:

It was the aim of this study to evaluate the activity and tolerance of gemcitabine and oxaliplatin in pretreated metastatic breast cancer patients.

METHODS:

Thirty-one patients who had disease relapse or progression after completion of an anthracycline- and/or taxane-based front-line regimen were treated with gemcitabine 1,500 mg/m(2) on days 1 and 8 as a 30-min intravenous infusion and oxaliplatin 130 mg/m(2) on day 8 as a 4-hour intravenous infusion, in cycles of 21 days.

RESULTS:

Complete response occurred in 1 patient (3%) and partial response in 4 patients (13%) (overall response rate 16%; 95% confidence interval 3.2-29.1). Nine patients (29%) had stable disease and 17 (55%) progressive disease. Three partial responses (13%) were achieved among 23 patients receiving the regimen as third-line treatment. The median duration of response was 6 months (range 3-44.8), the median time to tumor progression 4.6 months (range 0.8-43.8), and the median survival 14.4 months (range 2.1-44.8). Grade 3 and 4 neutropenia occurred in 14 patients (45%), grade 3 and 4 thrombocytopenia in 6 patients (20%), and grade 2 and 3 asthenia in 4 patients (13%). There was no episode of febrile neutropenia.

CONCLUSION:

The gemcitabine-oxaliplatin combination is a relatively active and well-tolerated salvage regimen in patients with heavily pretreated metastatic breast cancer.

Kakolyris S, Kalbakis K, Potamianou A, Malamos N, Vamvakas L, Christophillakis C, Tselepatiotis E, Giassas S, Mavroudis D, Amarantidis K, Georgoulias V.

INTRODUCTION:

To evaluate the efficacy and tolerance of biweekly paclitaxel and carboplatin combination in patients with castration-resistant prostate cancer.

PATIENTS AND METHODS:

Patients were treated with paclitaxel at the dose of 135 mg/m(2) followed by carboplatin AUC 3 on day 1 every 2 weeks in cycles of 28 days.

RESULTS:

Thirty-eight patients with castration-resistant prostate cancer were enrolled, and all of them had received frontline chemotherapy with docetaxel and prednisone, while 24 (63.2 %) had received 2 or more prior chemotherapy regimens. In an intention-to-treatment analysis, a clinical and/or biochemical response (>50 % decline) was observed in 10 patients (26.3 %; 95 % CI, 12.3-40.3 %), stable disease in 13 (34.2 %) and progressive disease in 15 (39.5 %). The median duration of response was 6.1 months (range, 1.0-9.8), the median time to tumor progression (TTP) 3.6 months (95 % CI, 2.1-5.2) and the median overall survival 9.9 months (95 % CI, 6.2-13.6). The probability for 1-year survival was 43 %. Grade 3 and 4 neutropenia was observed in three (7.9 %) and nine (23.7 %) patients, respectively.

CONCLUSION:

The biweekly administration of paclitaxel/carboplatin regimen in patients with castration-resistant prostate cancer is an active and well-tolerated regimen which merits to be further evaluated in the context of salvage treatment.

Kentepozidis N, Soultati A, Giassas S, Vardakis N, Kalykaki A, Kotsakis A, Papadimitraki E, Pantazopoulos N, Bozionellou V, Georgoulias V.

BACKGROUND:

A multicenter phase II study was conducted in order to evaluate the efficacy and safety of oxaliplatin as first-line treatment of patients with locally advanced or metastatic carcinoma of the biliary tract.

PATIENTS AND METHODS:

Twenty-nine chemo-naïve patients with locally advanced or metastatic biliary tract carcinoma received oxaliplatin 130 mg/m(2) i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity.

RESULTS:

An objective response (3 complete responses, 3 partial responses) was achieved in 6 patients (20.6%, 95% CI 5.95-35.4). Disease control (complete response, partial response and stable disease) was observed in 14 patients (48.2%). The median time to tumor progression was 3 months (range 0.7-39) and the median overall survival was 7 months (range 1-39). The 1-year survival rate was 32%. Toxicity was mild.

CONCLUSION:

Oxaliplatin is an active agent against biliary tract carcinoma and therefore should be further investigated in combination with other cytotoxic drugs.

Androulakis N, Aravantinos G, Syrigos K, Polyzos A, Ziras N, Tselepatiotis E, Samonis G, Kentepozidis N, Giassas S, Vamvakas L, Georgoulias V.

PURPOSE:

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment for patients with peritoneal carcinomatosis (PC). Our objective was to identify new prognostic factors within the Peritoneal Cancer Index (PCI) score in PC patients.

METHODS:

140 patients (60 ovarian, 45 colon, 14 gastric, 10 pseudomyxoma peritonei, 5 mesothelioma, 6 sarcoma) with PC treated with CRS+HIPEC from 2007 to December 2013 were retrospectively included. Tumor extent and location were assessed by the PCI and residual disease was recorded using the Completeness of Cytoreduction (CC) score. All clinical data were computed in univariate and multivariate analysis using survival as primary endpoint.

RESULTS:

The PCI remains the most important factor concerning the long-term survival. Involved areas 4, 5 and 8 are more favorable in survival vs areas 9, 10 and 11, which predict a significantly worse outcome (p<0.002). Prognosis varies not only depending on how many peritoneal areas are involved but also on the location of the primary tumor.

CONCLUSION:

We demonstrated that the involvement of different areas in the PCI system has a significant impact on the final prognosis and survival.

Spiliotis J, Halkia EE, Kalantzi N, Giassas S, Lianos E, Efstathiou E, Sugarbaker PH.

PURPOSE:

The combination of irinotecan and cisplatin (IP) has shown at least comparable efficacy to that of etoposide/cisplatin (EP) in patients with extensive-stage small cell lung cancer. We conducted a phase II study to evaluate the efficacy and tolerance of EP regimen followed by thoracic radiotherapy (TRT) and IP consolidation chemotherapy in patients with limited-stage small cell lung cancer.

PATIENTS AND METHODS:

Thirty-three chemotherapy-naive patients with limited-stage small cell lung cancer (LS-SCLC) were treated with etoposide 100mg/m(2) on days 1-3 and cisplatin 80mg/m(2) on day 1. Radiotherapy was given 3 weeks after the first treatment cycle concurrently with weekly cisplatin 20mg/m(2) on day 1 and etoposide 50mg/m(2) on day 4 within 5-6 weeks, followed by three courses of irinotecan 60mg/m(2) on days 1, 8, and 15 and cisplatin 60mg/m(2) on day 1 of a 4-week cycle.

RESULTS:

There were no treatment-related deaths. Toxicities during chemo-radiotherapy were mild including grade 3/4 neutropenia (24%) and grade 2 esophagitis (6%). The major toxicity observed during consolidation chemotherapy was grades 3-4 neutropenia which affected 42% of patients. In an intention-to-treat analysis the overall response rate was 66% (CR: 30% and PR: 36%). After a median follow-up period of 35.7 months (range: 9.6-41.2 months), the median survival time was 19 months (95% CI: 14.5-23.5 months), the median time to tumor progression 8.3 months and the 1- and 2-year survival rates 72% and 27.5%, respectively.

CONCLUSIONS:

Consolidation chemotherapy with IP following concurrent EP plus TRT is a safe and with acceptable toxicity regimen and deserves further phase III testing in patients with LS-SCLC.

Xenidis N, Kotsakis A, Kalykaki A, Christophyllakis Ch, Giassas S, Kentepozidis N, Polyzos A, Chelis L, Vardakis N, Vamvakas L, Georgoulias V, Kakolyris S.

PURPOSE:

To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of weekly high dose 5-fluorouracil (5FU) continuous infusion and leukovorin (LV) alternatively combined with oxaliplatin and irinotecan in patients with advanced tumors of the gastrointestinal (GI) tract.

PATIENTS AND METHODS:

Patients received a fixed dose of LV (500 mg/m(2)) over 2 h infusion on weeks 1 to 4 and escalated doses of: oxaliplatin (starting dose 65 mg/m(2): 120 min i.v. infusion on weeks 1 and 3); irinotecan (starting dose 80 mg/m(2); 90 min i.v. infusion on weeks 2 and 4) and 5FU (starting dose 1500 mg/m(2); 22 h continuous i.v. infusion, on weeks 1 to 4), in cycles of 5 weeks. DLTs were evaluated during the fi rst cycle.

RESULTS:

Twenty-eight patients were treated on 8 dose levels and all but two patients received the regimen at least as second-line treatment. The DLT level was reached at the oxaliplatin dose of 90 mg/m(2), irinotecan dose of 110 mg/m(2), LV dose of 500 mg/m(2) and 5FU dose of 1750 mg/m(2); the recommended MTDs were 85 mg/m(2) for oxaliplatin, 110 mg/m(2) for irinotecan, 1750 mg/m(2) for 5FU and 500 mg/m(2) for LV. Grade 3 or 4 diarrhea and grade 3 nausea/vomiting were the dose-limiting events. Diarrhea was the most common toxicity of the regimen, occurring in 12 (42.8%) patients. Hematological toxicity was mild and there were no treatment- related deaths.

CONCLUSION:

This weekly regimen showed a favorable toxicity profile and merits further investigation in patients with advanced/metastatic tumors of the GI tract.

Gkioulbasanis I, Souglakos J, Vardakis N, Kotsakis A, Saridaki Z, Kentepozidis N, Polyzos A, Giassas S, Ignatiadis M, Bozionelou V, Christophylakis C, Georgoulias V.

BACKGROUND:

The current treatment of ovarian cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second- or third-line systemic chemotherapy afterward.

METHODS:

In an 8-year period (2006-2013), 120 women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] IIIc and IV) who experienced disease recurrence after initial treatment with conservative or debulking surgery and systemic chemotherapy were randomized into two groups. Group A comprised 60 patients treated with CRS followed by HIPEC and then systemic chemotherapy. Group B comprised 60 patients treated with CRS only and systemic chemotherapy.

RESULTS:

The mean survival for group A was 26.7 versus 13.4 months in group B (p < 0.006). Three-year survival was 75 % for group A versus 18 % for group B (p < 0.01). In the HIPEC group, the mean survival was not different between patients with platinum-resistant disease versus platinum-sensitive disease (26.6 vs. 26.8 months). On the other hand, in the non-HIPEC group, there was a statistically significant difference between platinum-sensitive versus platinum-resistant disease (15.2 vs. 10.2 months, p < 0.002). Complete cytoreduction was associated with longer survival. Patients with a peritoneal cancer index score of <15 appeared also to have longer survival.

CONCLUSIONS:

The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with recurrence in an initially advanced ovarian cancer.

Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, Giassas S.

PURPOSE:

Temozolomide, a novel triazene derivative, has shown activity in vitro against lung cancer as well as against brain metastases from a variety of solid tumors including non-small cell lung cancer (NSCLC). The aim of the study was to evaluate the efficacy and safety of temozolomide in pretreated patients with NSCLC.

PATIENTS AND METHODS:

Thirty-one pretreated patients (median age 60 years) with histologically confirmed NSCLC were enrolled. Sixteen (52%) patients had a performance status (ECOG) of 0-1, 12 (39%) had pretreated brain metastases and 28 (90.3%) had received >2 lines of treatment. Temozolomide was administered at a dose of 75 mg/m(2) daily for 21 days every 28 days. A total of 73 chemotherapy cycles were administered.

RESULTS:

In an intention-to-treat analysis, 2 patients (6.5%; 95% CI: -2.2 to 15.1%) achieved a partial response and 3 (10%) stable disease. The median time to progression was 2.4 months, the median survival time 3.3 months and the 1-year survival rate 22.5%. There was a toxic death due to grade 4 neutropenia. Grade 3 and 4 lymphopenia occurred in 4 (13%) and 2 (6%) patients, respectively. Nonhematological toxicity was mild, consisting of grade 2-3 asthenia (n = 14 patients) and grade 3 diarrhea (n = 1 patient).

CONCLUSION:

Prolonged low daily doses of temozolomide demonstrate minimal activity as salvage therapy in patients with advanced NSCLC. The combination of low daily doses of temozolomide with other anticancer drugs probably merits further evaluation.

Kouroussis C, Vamvakas L, Vardakis N, Kotsakis A, Kalykaki A, Kalbakis K, Saridaki Z, Kentepozidis N, Giassas S, Georgoulias V.

BACKGROUND:

The purpose of this study was to evaluate the efficacy of erlotinib as front-line treatment in clinically selected patients with non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Forty-nine previously untreated white patients who had stage IIIB/IV pulmonary adenocarcinoma or bronchoalveolar carcinoma and who were nonsmokers or former light smokers were treated with erlotinib 150 mg daily, irrespective of the EGFR mutation status.

RESULTS:

In an intention-to-treat analysis, the overall response rate (ORR) was 24.5%. The median progression-free survival (PFS) was 6.7 months, the median overall survival (OS) was 15.5 months, and the 1-year survival rate was 61.3%. Among the 36 patients for whom tumor material was available, 9 (25%) had activating EGFR mutations. The ORR was 66.7% in patients with activating EGFR mutations and 14.8% in patients with wild-type EGFR (2P = .006). In patients with activating EGFR mutations, the OS has not been reached, whereas it was 12.9 months in patients with EGFR wild type (2P = .045). Twenty-four patients had a PFS of > 6 months; 11 (45.8%) of them had EGFR wild type and 7 (29.1%) had EGFR mutation.

CONCLUSIONS:

The selection of patients for treatment with EGFR-directed tyrosine kinase inhibitors (TKIs) should be based on mutation testing. However use of clinical (smoking status) and pathologic (adenocarcinoma) criteria may identify a subgroup of patients with advanced/metastatic NSCLC who can benefit from front-line treatment with erlotinib when mutation testing is not feasible.

Pallis AG, Voutsina A, Kentepozidis N, Giassas S, Papakotoulas P, Agelaki S, Tryfonidis K, Kotsakis A, Vamvakas L, Vardakis N, Georgoulias V.