Performance evaluation of the Abbott CELL-DYN Emerald for use as a bench-top analyzer in a research setting.

INTRODUCTION: The CELL-DYN Emerald is a compact bench-top hematology analyzer that can be used for a three-part white cell differential analysis. To determine its utility for analysis of human and mouse samples, we evaluated this machine against the larger CELL-DYN Sapphire and Sysmex XT2000iV hematology analyzers. METHODS: 120 human (normal and abnormal) and 30 mouse (normal and abnormal) samples were analyzed on both the CELL-DYN Emerald and CELL-DYN Sapphire or Sysmex XT2000iV analyzers. For mouse samples, the CELL-DYN Emerald analyzer required manual recalibration based on the histogram populations. RESULTS: Analysis of the CELL-DYN Emerald showed excellent precision, within accepted ranges (white cell count CV% = 2.09%; hemoglobin CV% = 1.68%; platelets CV% = 4.13%). Linearity was excellent (R² ≥ 0.99), carryover was minimal (<1%), and overall interinstrument agreement was acceptable for both human and mouse samples. Comparison between the CELL-DYN Emerald and Sapphire analyzers for human samples or Sysmex XT2000iV analyzer for mouse samples showed excellent correlation for all parameters. CONCLUSION: The CELL-DYN Emerald was generally comparable to the larger reference analyzer for both human and mouse samples. It would be suitable for use in satellite research laboratories or as a backup system in larger laboratories.

Carboplatin/gemcitabine alternating with carboplatin/pegylated liposomal doxorubicin and carboplatin/cyclophosphamide in platinum-refractory/resistant paclitaxel - pretreated ovarian carcinoma.

OBJECTIVE: In this phase II study the efficacy and toxicity of an alternating chemotherapy regimen was examined in platinum-resistant relapsed epithelial ovarian cancer (EOC) patients. METHODS: Forty-five patients with platinum-refractory/resistant relapsed EOC, previously treated with carboplatin+paclitaxel+/-epirubicin were included. The regimen was consisted of gemcitabine 800 mg/m(2) (days 1+8) and carboplatin AUC 5, alternating with pegylated liposomal doxorubicin 30 mg/m(2) and carboplatin AUC 5, alternating with carboplatin AUC 5 and cyclophosphamide 600 mg/m(2), every 3 weeks for a total of 9 cycles. RESULTS: Among 38 patients with measurable disease, 39.4% (95% CI: 23.2-55.7) responded (five complete response and 10 partial response), while 30 out of 40 (75%) patients assessable by CA125 criteria had a serological response. Responses were more frequent in patients with platinum-free interval (PFI) 3-6 months than in those with PFI 0-3 months, but this was not statistically-significant. After a median follow-up of 19.5 months (range, 1.0-37+ months) the median progression-free survival was 7.1 months (95% CI: 3.4-10.8) and the median survival (OS) was 18.8 months (95% CI: 15.6-22.0). For patients with PFI 0-3 months PFS was 4.3 (95% CI: 0.8-7.8) months, while for those with PFI 3-6 months PFS was 8.9 (95% CI: 5.3-12.4) months (p=0.062). The regimen was well-tolerated and the main grade 3-4 toxicity was myelosuppression, palmar-plantar erythrodysesthesia, allergy and fatigue. CONCLUSION: This alternating regimen, including carboplatin, gemcitabine, liposomal doxorubicin and cyclophosphamide, is an active and well-tolerated treatment in platinum relapsed/refractory EOC patients.

Rule based processing of the CD4000, CD3200 and CD Sapphire analyser output using the Cerner Discern Expert Module.

The latest version of our Laboratory Information System haematology laboratory expert system that handles the output of Abbott Cell-Dyn Sapphires, CD4000s and a CD3200 full blood count analyser in three high-volume haematology laboratories is described. The three hospital laboratories use Cerner Millennium Version 2007.02 software and the expert system uses Cerner Millennium Discern Expert rules and some small Cerner Command Language in-house programs. The entire expert system is totally integrated with the area-wide database and has been built and maintained by haematology staff members, as has the haematology database. Using patient demographic data, analyser numeric results, analyser error and morphology flags and previous results for the patient, this expert system decides whether to validate the main full blood count indices and white cell differential, or if the analyser results warrant further operator intervention/investigation before verifying, whether a blood film is required for microscopic review and if abnormal results require phoning to the staff treating the patient. The principles of this expert system can be generalized to different haematology analysers and haematology laboratories that have different workflows and different software.

Microvessel density (MVD) and cyclooxygenase-2 (COX-2)/ beta-catenin interaction are associated with relapse in patients with transitional carcinoma receiving adjuvant chemotherapy with paclitaxel/carboplatin: a hellenic cooperative oncology group (HECOG) study.

BACKGROUND: Cycloxygenase (COX)-2 has been associated with proliferation, apoptosis and angiogenesis in urothelial cancer. The prognostic significance of COX-2 in patients who received adjuvant chemotherapy for urothelial cancer was examined. PATIENTS AND METHODS: Expression of COX-2, p53, ki67, beta-catenin, vascular endothelial growth factor (VEGF) and microvessel density (MVD) were studied retrospectively in 59 patients with urothelial cancer (pT3, pT4, N+) who had undergone surgery. The patients had subsequently received adjuvant chemotherapy. RESULTS: Thirty-eight out of 59 cases (64%) were positive for COX-2. COX-2 was not associated either with progression-free survival (PFS) or overall survival (OS). MVD levels > or =47 were associated with longer median PFS compared with lower levels (not reached vs. 13 months [95% CI: 8-18], p=0.048). The median PFS for patients with beta-catenin nuclear accumulation and COX-2 expression was 6 months (95% CI: 4-7) compared with 19 months (95% CI: 14-23) for neither or only one of these factors (p=0.018). CONCLUSION: MVD may be a useful indicator of relapse in high-risk urothelial cancer treated with adjuvant chemotherapy.

Primary ovarian lymphoma: report of two cases and review of the literature.

Ovarian lymphoma is a rare entity. Clinicians should be aware of its clinical manifestations and management since surgery alone often is not adequate treatment. Here, we present two cases of ovarian lymphoma and discuss what is known about ovarian lymphoma.

Carboplatin and paclitaxel in advanced or metastatic endometrial cancer.

OBJECTIVES: The purpose of this study was to evaluate the activity and toxicity of carboplatin and paclitaxel combination in advanced or recurrent endometrial carcinoma. METHODS: Forty-seven eligible patients with measurable advanced or recurrent endometrial carcinoma were treated with carboplatin [area under the curve (AUC) 5] and paclitaxel 175 mg/m(2) every 3 weeks for 6-9 cycles or until disease progression or unacceptable toxicity. RESULTS: There were 10 complete responses (CRs) (21%) and 19 partial responses (PRs) (41%) for an overall response rate (RR) of 62% (29 patients) (95% confidence interval [CI], 47-76%). The median progression-free survival (PFS) was 15 months (95% CI, 7.3-22.7 months) and the median overall survival (OS) was 25 months (95% CI, 19.0-31.0 months). No difference was found in RR and OS in patients with primary advanced disease and those with recurrent tumors. Similarly, no difference was found in PFS and OS for patients with serous/clear tumors and those with endometrioid tumors. Toxicity was generally mild except for myelotoxicity. Neutropenia grade 3/4 was recorded in 36% of patients and 6% experienced febrile neutropenia. One patient each developed grade 4 thrombocytopenia and anemia. Grade 3 sensory neuropathy was recorded in 6% of patients. CONCLUSION: The combination of carboplatin and paclitaxel appears to have activity in advanced or recurrent endometrial carcinoma with an acceptable toxicity profile.

Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer. A phase III study of the Hellenic Cooperative Oncology Group.

BACKGROUND: This phase III study was designed to compare the combination paclitaxel (Taxol)-gemcitabine (PG) versus carboplatin-gemcitabine (CG) in patients with advanced inoperable non-small-cell lung cancer. METHODS: Chemotherapy-naive patients with performance status of zero or one were randomized to gemcitabine 1 gm/m(2) on days 1 and 8 plus either paclitaxel 200 mg/m(2) on day 1 (arm A) or carboplatin at an area under the concentration-time curve of 6 mg on day 1 (arm B) every 3 weeks. Primary end point was overall survival (OS). Secondary end points included objective response (OR), time to progression and toxicity. RESULTS: A total of 512 patients were enrolled and 452 eligible (arm A, 225; arm B, 227) were analyzed. All characteristics were well balanced with the exception of vena cava obstruction symptoms and lymph node involvement. Median survival was 9.97 months [95% confidence interval (CI) 8.74-12.0] for group A and 10.49 (95% CI 9.04-11.94) for group B. There was no difference in the OS, 1-year survival, OR and TtP. However, statistically significant differences were seen in toxicity. CONCLUSION: The two regimens are equally active. Myelotoxicity is worse in the CG group whereas alopecia, myalgia and neurotoxicity worse in the PG group.

Multicenter phase-II trial of irinotecan plus oxaliplatin [IROX regimen] in patients with poor-prognosis cancer of unknown primary: a hellenic cooperative oncology group study.

BACKGROUND: Cancer of unknown primary (CUP) lacks established therapy although it affects 3% of cancer patients. We evaluated the irinotecan-oxaliplatin combination (IROX regimen) in previously untreated patients with non-favorable subsets of unknown primary carcinomas. METHODS: This was a multicenter phase-II trial. Protocol treatment consisted of oxaliplatin 80 mg/m(2) followed by irinotecan 160 mg/m(2) administered every 3 weeks. The primary end points were response rate and toxicity, and secondary end points were time to progression and survival. RESULTS: Forty-seven patients with liver, bone or multiple visceral metastases entered into the trial and received a median 6 chemotherapy cycles (1-11). The regimen was very well tolerated with one febrile neutropenia case and six cases with diarrhea grade 3 (16%). In intent-to-treat analysis the tumor response rate was 13% (95% CI = 4.8-25.7%) and 12 patients (27%, 95%CI 13.9-40.4%) had at least 4 months' duration of disease stabilization. The median time to progression was 2.7 months and the median survival was 9.5 months, with 40% of patients alive at 1 year. CONCLUSIONS: The IROX regimen demonstrated similar efficacy and a favorable toxicity profile compared to other more toxic chemotherapy combinations in patients with poor-prognosis CUP.

Low-grade mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 97 patients by the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: The aim was to examine characteristics and treatment results of patients with mucosa-associated lymphoid tissue (MALT) non-Hodgkin's lymphomas. PATIENTS AND METHODS: Epidemiological and clinical features of 97 patients with MALT lymphoma from the Hellenic Cooperative Oncology Group registry were analysed retrospectively for their prognostic significance in progression-free survival (PFS) and overall survival (OS). Comparisons were made between patients with gastric and nongastric sites of primary lymphoma and between different therapeutic modalities. RESULTS: Sixty-five patients presented with gastric and 32 with nongastric lymphomas. The most frequent locations of nongastric lymphomas were the bowel, lung and parotid. Gastric lymphomas occurred more frequently in males and younger patients compared with nongastric lymphomas. Seventy-four per cent of patients had early (Ann Arbor stages I-II) and 26% had advanced (stages III-IV) disease. The median PFS for the entire population was 44 months. At 5 years, 47% of patients were progression free and the OS rate was 80%. The most reliable prognostic factor for PFS and OS was the Ann Arbor stage; 5-year PFS was 67% versus 13% and 5-year OS 91% versus 51% for patients with early versus advanced disease, respectively (P < 0.001). Of the patients treated with chemotherapy only, 87% achieved an objective response and 71% complete response. Surgery did not offer survival benefit compared with chemotherapy in localised gastric lymphoma. CONCLUSION: MALT lymphomas represent a distinct disease entity with widespread extranodal origin, indolent clinical course and high chemosensitivity. Ann Arbor stage was the most reliable prognostic and predictive factor.

Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00.

BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.

Mitoxantrone plus vinorelbine in pretreated patients with metastatic breast cancer.

Vinorelbine and mitoxantrone have both been demonstrated to have significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with metastatic breast cancer (MBC). Fifty-one previously treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were eligible for evaluation. Median age was 59 years (range 33-82) and ECOG performance status was < or =2. Distant sites of metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine 20 mg/m(2), D1+8 and mitoxantrone 10 mg/m(2) D8 every 21 days for 6 cycles. All eligible patients were analyzed for toxicity and response. Two patients (4%) achieved complete response and 12 (25.5%) partial response. The objective overall response rate was 29.5% (95% confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive disease and 7 (15%) were non-evaluable. After a median follow up of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to disease progression was 5 months (range 1 - 32). A total of 280 cycles was delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths. The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer.

CEOP-21 versus CEOP-14 chemotherapy with or without rituximab for the first-line treatment of patients with aggressive lymphomas: results of the HE22A99 trial of the Hellenic Cooperative Oncology Group.

BACKGROUND: In this study we investigated whether administering CEOP (cyclophosphamide, epirubicin, vincristine [Oncovin], and prednisone) every 2 weeks (CEOP-14) instead of every 3 weeks (the standard CEOP-21 regimen) improves outcomes in patients with previously untreated aggressive lymphomas. In a secondary analysis we evaluated the impact of adding rituximab to CEOP-14/CEOP-21 chemotherapy. STUDY DESIGN: The trial opened in March 1999, and patients were randomly assigned to either CEOP-14 or CEOP-21. All patients enrolled from May 2002 onward received rituximab with each chemotherapy cycle, and those attaining a complete response received rituximab consolidation. RESULTS: Complete and overall response rates in the CEOP-21 +/- rituximab (N = 114) and CEOP-14 +/- rituximab (N = 103) arms were similar, as were the overall survival (P = 0.769) and time to progression distributions (P = 0.969). Rituximab was shown to have a beneficial effect both on the overall survival and on the time to progression. CONCLUSIONS: Thus far, no significant improvement in outcome has been demonstrated with CEOP-14 +/- rituximab versus CEOP-21 +/- rituximab. However, with addition of rituximab to CEOP-21/CEOP-14, significant improvements in time to progression and overall survival were achieved.

Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy.

The current prospective study sought to trace the incidence and severity of cisplatin plus paclitaxel (DDP+P)-induced neuropathy and to determine its clinical and electrophysiological pattern. Furthermore, it was attempted to describe its evolution by following up the course of peripheral neuropathy (PN) during chemotherapy as well as 3 months after its discontinuation. Thirteen adult patients scheduled to be treated with six courses of cumulative DDP+P-based regimens for a non-myeloid malignancy participated in this study. These patients were clinically and electrophysiologically monitored at baseline, during chemotherapy and 3 months after its discontinuation. The severity of PN was summarized by means of a modified PN score. Evidence of PN was disclosed in nine of the 13 patients (69.2%). The mean PN score for patients that manifested some grade of PN was 17.3 +/- 6.1 (range 9-28). All longitudinal comparisons concerning the motor conduction velocities (MCV) variables failed to reach significance. By contrast, comparisons of the mean changes at baseline and each of the follow-up studies revealed a significant decrease in all sensory action potentials examined. The follow-up evaluation performed 3 months after the discontinuation of chemotherapy showed that the DDP+P-induced neuropathy persists and progresses over time. Our results indicate that the majority of patients treated with a DDP+P-based regimen at full dose intensities would manifest an axonal, predominately sensory PN, of mild to moderate severity, which would persist for several months after the discontinuation of chemotherapy.

Survival improvement of young patients, aged 16-23, with Hodgkin lymphoma (HL) during the last three decades.

The prognostic factors, treatments and outcomes of 55 young adults (16-23 years old) with Hodgkin lymphoma (HL) treated in the Second Department of Internal Medicine Propaedeutic, Medical Oncology Unit, Athens University, over the past 25 years, are reviewed. Patients were treated with the chemotherapy regimens available at each time period which were MOPP (Group A; 1978-1987), MOPP/ABVD (Group B; 1988-1993) and BEACOPP or ABVD (Group C; 1994-2003). The eligible patients, received radiotherapy (RT) according to treatment consensus. Additionally, the patients were retrospectively divided according to risk factors (abnormal erythrocyte sedimentation rate (ESR), bulky mediastinal disease, > 3 involved nodes and extranodal involvement) into low [stage I/II; five patients (9%)], intermediate [stage III with adverse prognostic factors; 18 patients (33%)] and high risk categories [stages IIB bulky and III/IV; 32 patients (58%)]. A total of 21 (38%) patients experienced relapse (three intermediate and 19 high risk). The 5-year survival and the 5-year event free survival (EFS) figures were Group A: 65% and 53%, Group B: 80% and 65%, Group C: 100% and 88.5%, respectively, the improvements between Group B and C were statistically significant (p = 0.04 and p = 0.005, respectively) among the three time periods. The overall survival (OS) and EFS differed significantly between intermediate and high risk categories (OS: p = 0.04, EFS: p = 0.005). The sequential use of RT did not influence OS and EFS but there was a trend of improvement with RT in the later periods. Survival of young patients with HL is significantly improving most probably due to improved chemotherapy treatment and understanding of the risk factors. Current controversial issues surrounding this disease, including the role of radiotherapy, positron emission tomography (PET), bone marrow biopsy and stem cell transplantation are discussed.

Cisplatin-based chemotherapy for merkel cell carcinoma of the skin.

PURPOSE: Merkel cell carcinoma (MCC), a rare tumor of the skin with aggressive behavior, is usually fatal when advanced disease is present. The role of chemotherapy (CT) in the treatment of patients with MCC is unclear. METHODS: Over 15 years, 9 patients with locally advanced or metastatic disease were treated with carboplatin (CBDCA) (300 mg/m(2) of AUC 5 on Day 1) and etoposide (VP-16) (100 mg/m(2) on Days 1-3) every 3 weeks. As second-line CT, cisplatin (CDDP) (60-100 mg/m(2)), ifosfamide (IFO) (3-5 g/m(2)) and epirubicin (EPI) (30-50 mg/m(2)) were utilized. RESULTS: Of the 3 patients who received adjuvant therapy, one achieved complete response after 108+ months with second-line chemotherapy and radiotherapy, despite a brief relapse; 2 patients remain disease-free after 84+ and 108+ months. Of the 6 patients with locally advanced or metastatic disease who were treated with first-line chemotherapy, one (16.6 percent) achieved a complete response and 3 (50 percent) achieved partial response, for an overall response rate of 66.6 percent. Two patients (one with complete and one with partial response) received subsequent radiotherapy, following which complete response was achieved. Of the 2 complete responders, one patient remains disease-free after 56+ months. The median overall survival from the time of initial diagnosis for the whole group was 56 months (range 15-114 months); the median overall survival from the initiation of chemotherapy was 18 months (range 6-108+). Local recurrences and soft tissue metastases responded better than visceral metastases. Patients with partial response and no response had rapid disease progression and fatality, despite second-line chemotherapy and/or radiotherapy. CONCLUSION: MCC appears to be chemosensitive but can progress rapidly with fatal outcomes. Although the rarity of these tumors precludes randomized trials, a common treatment plan should be utilized by those treating MCC. This may allow some conclusions regarding the optimum treatment of patients with MCC to be drawn in the future.

Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group.

BACKGROUND: In the present phase II multicenter study, we assessed the efficacy and tolerability of the combination of gemcitabine and carboplatin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, locally advanced or metastatic pancreatic cancer were treated with gemcitabine 800 mg/m(2) on days 1 and 8 and carboplatin at an AUC of 4 on day 8 of a 3-week cycle, for a total of six cycles. Primary end points were response rate and clinical benefit; secondary end points were, survival, time to progression (TTP) and toxicity. RESULTS: A total of 50 patients were enrolled in the study, 47 of whom were eligible for treatment. The median age was 63 years (range 34-76) and the median Karnofsky performance status (PS) was 80%. Patients received a median of six cycles (range 1-11). Among 35 patients evaluable for response, eight (17%) achieved partial response; 15 (32%) and 12 (25%) patients had stable and progressive disease, respectively. The median overall survival was 7.4 months; the median TTP was 4.4 months and the 1-year survival was 28%. The observed clinical benefit response was remarkable. After the second cycle of chemotherapy, 21 of 31 (68%) patients experienced pain improvement and reduced analgesic consumption. At the same time, 35% and 56% of our patients significantly improved their Karnofsky PS and weight, respectively. Overall, the treatment was well tolerated. The most common grade 3-4 toxicities were hematological, including 8% anemia, 6% neutropenia and 13% thrombocytopenia. CONCLUSIONS: The combination of gemcitabine plus carboplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer. This regimen has an acceptable toxicity profile and provides a significant clinical benefit, and hence warrants further investigation.

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial.

BACKGROUND: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks. RESULTS: A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm. CONCLUSIONS: The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.

Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group.

PURPOSE: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. PATIENTS AND METHODS: Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. RESULT: Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. CONCLUSION: MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.

Treatment of intermediate and advanced stage Hodgkin's disease with modified baseline BEACOPP regimen: a Hellenic Co-operative Oncology Group Study.

The purpose of this prospective phase II trial was to investigate the safety and efficacy of a modified baseline BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen in the treatment of intermediate and advanced stage Hodgkin's disease (HD). From October 1997 to November 2001, 51 consecutive, previously untreated patients with stage IIA (bulky), IIB, III, and IV disease were treated with a modified baseline BEACOPP regimen with the etoposide administered i.v. on day 1 and orally at a dose of 100 mg/m2, on days 2 and 3. Each patient was scheduled to receive eight courses of BEACOPP with consolidation radiotherapy to bulky (> or =5 cm) or residual disease. There were 25 males and 26 females with a median age of 32 yr (16-65 yr); 80.3% of the patients had nodular sclerosis HD, 41% had bulky disease (> or =5 cm), 10 were in stage IIA (bulky > or =10 cm), 15 in stage IIB, 19 in stage III, and seven in stage IV. Thirty-seven patients (72.5%) achieved a complete response and 17.6% partial response. No significant difference in overall response rate was observed between patients with: (i) 0-2 vs. > or =3 negative prognostic factors, (ii) in stage II vs. stages III/IV, LDH level, and bulky disease. With a median follow up period of 39.5 months, actuarial 3-yr survival rate is 82% and time to progression rate 72.5%. Treatment with this combination was well tolerated. Grades 3 and 4 leukopenia and neutropenia occured in 26% and 28% of the patients, respectively, whereas in 16.3% of the patients infection was observed. Support with granulocyte colony-stimulating factor was given to 59% of the patients. No case of secondary MDS/leukemia has been observed. The results of the present study demonstrate that the modified baseline BEACOPP regimen with radiotherapy used in our patients was well tolerated and effective therapy for intermediate and advanced stage HD. Further follow up time is required to evaluate long-term toxicity.

Monoclonal gammopathies in B-cell non-Hodgkin's lymphomas.

The association of monoclonal gammopathy (MG) with B-cell non-Hodgkin's lymphomas (NHL) is a well known phenomenon. The aim of the present work was to study the incidence, type of monoclonal component and prognostic significance of MG in a population of 255 cases with B-cell NHL. Among 255 evaluable patients with B-cell NHL, 145 were males and 110 females with a median age of 58 years (range 18-85). There were 166 patients with the various subtypes of aggressive (intermediate/high grade) NHL and 89 with the various subtypes of low risk. MG was detected in 44 patients (17.2%) with a median age of 61 years (range 23-79). There were 22 cases (8.6%) with IgG type (IgG/(k) 15, IgG/(lambda) 7), 4 cases (1.6%) with (IgA/(k) 3, IgA/(lambda) 1) and 18 cases (7.0%) with IgM (IgM/(k) 12 IgM/(lambda) 6). MG was found in 15.6% of the patients with aggressive NHL, while in low risk NHL the incidence was 20.2% (N.S.). The type of MG according to histological classification was as follows: Aggressive NHL: IgG 17 cases, IgA 2 cases, IgM 7 cases: low risk NHL: IgG 5 cases, IgA 2 cases, IgM 11 cases. The distribution of MG according to stage of the disease was as follows: stage I (4.5%), stage II (18%), stage III (6.8%) and stage IV (70.4%). The median survival of patients with aggressive NHL with MG was 17 months compared to 40 months of those without (P=0.22). Similarly the median survival of patients with low risk NHL and MG was 51.5 months compared to 38.5 months of those without (P=0.90). In conclusion MG was detected in 17.2% of cases with B-cell NHL. IgG-MG was more frequent in cases with aggressive NHL, while IgM in cases with low risk NHL. MG was mostly associated with advanced stage and had not any prognostic significance on survival.