Dimitrios Mitsibounas

Treatment of Waldenstrom's macroglobulinemia with the combination of fludarabine and cyclophosphamide

Fludarabine is an active agent for the treatment of Waldenstroms macroglobulinemia (WM) and its combination with cyclophosphamide has been effective in many patients with low-grade lymphoma and chronic lymphocytic leukemia. Based on these data, we administered the combination of fludarabine (25 mg/m 2 IV day 1-3) and cyclophosphamide (250 mg/m 2 IV day 1-3,) to 11 patients with WM. Most patients had features indicating poor prognosis including median age of 73 years (range 60-84 years), hemoglobin <100 g/l in 73%, B 2 -microglobulin >3 mg/l in 64%, symptomatic hyperviscosity in 55% of patients. Only 2 patients were previously untreated, 7 were primary refractory and 2 were relapsing on treatment. The fludarabine-cyclophosphamide combination (FC) was administered every 4 weeks for a total of four courses. Partial response, defined by at least 50% reduction of serum monoclonal protein and of tumor infiltrate at all involved sites was documented in 6 patients (55%) (The median time to response was 4 months). Responding patients demonstrated resolution of disease-related symptoms and correction of anemia. Median time to progression for all patients was 24 months. With a mean follow-up of 28 months, two of six responding patients have progressed so far. The probability of 2-year survival is 70%. This regimen was relatively well tolerated. Complications included neutropenia grade 3 or 4 in 3 patients and thrombocytopenia grade 3 or 4 in 2 patients. There were five infectious episodes including two episodes of neutropenic fever. We conclude that the FC combination appears to be active in patients with WM most of whom were resistant to treatment and had poor prognostic factors. The addition of rituximab to FC requires further investigation.

Outpatient Treatment of Neutropenic Fever with Oral Antibiotics and Granulocyte Colony-Stimulating Factor

In recent years, several cancer patients who developed neutropenic fever were effectively treated on an outpatient basis with either intravenous or oral antibiotics. This approach is associated with reduced cost and improved patient convenience. However, the appropriate antibiotic regimen and the role of growth factors have not been established yet. In order to address these issues we performed a nonrandomized phase II study to assess the feasibility and efficacy of an oral antibiotic regimen in combination with granulocyte colony-stimulating factor (G-CSF) for the outpatient treatment of cancer patients with low-risk neutropenic fever. In 50 patients with solid tumors or lymphoma, 60 episodes of neutropenic fever were treated with the combination of oral ofloxacin 400 mg twice a day, oral amoxicillin 1 g 3 times a day and G-CSF 5 μg/kg/day subcutaneously. Patients receiving G-CSF prophylaxis were eligible for our study. Oral antibiotics were administered for at least 5 days and G-CSF was continued until resolution of neutropenia. Our patients were ambulatory, hemodynamically stable, and without significant comorbidity. Our combination was successful in 57 episodes (95%) with a median time for fever resolution of 3 days (range: 1–5 days). There was no significant toxicity associated with the antibiotic regimen with the exception of one case of reversible renal impairment. The role of G-CSF in the success of our antibiotic treatment is highly questionable since one half of our patients developed fever while on G-CSF prophylaxis. The combination of oral ofloxacin and amoxicillin with G-CSF is highly effective for the outpatient treatment of cancer patients who develop uncomplicated febrile neutropenia. The relative contribution of G-CSF needs clarification with a prospective randomized study.

Cardiac Tamponade Rapidly Evolving Toward Constrictive Pericarditis and Shock as a First Manifestation of Noncardiac Cancer

Abstract  A 44‐year‐old man presented with symptoms and signs of cardiac tamponade. Cytologic examination of the pericardial fluid was negative for malignancy and no manifestations of primary tumor were detected. Two weeks after pericardiocentesis the patient developed constrictive pericarditis. An emergency exploratory thoracotomy revealed a thick, fibrotic pericardium firmly adherent to the underlying myocardium. Histologic examination of the pericardium showed the presence of an adenocarcinoma, suspected to be a metastatic dissemination from a primary pulmonary source. The lymphatic spread of the tumor to the heart may explain the early development of pericardial effusion without malignant cells and the later development of pericardial and epicardial thickening. Cardiac tamponade of unknown origin should prompt a search for metastatic carcinoma, including in presence of a negative cytology. (J Card Surg 2004;19:134‐135)

Smoking among high school students.

Introduction: There are no recent data on smoking habits of high-school students in Greece. The primary objective of the study was to determine these epidemiological factors. Methods: The smoking habits of 927 high-school students (471 boys and 456 girls), aged between 15–18 years, in four regions of a Greek area (the island of Cos), were examined. Study data were collected using a questionnaire. Results: It was found that 32.48% of boys and 27.19% of girls are smokers; 43.3% had started smoking before the age of 14. The mean age for starting smoking was 14.4 ± 1.9 years for the boys and 14.9 ± 1.6 years for the girls. As many as 22.8% of the students smoke 6 to 10 cigarettes per day and 21.5% 16 to 20 cigarettes per day; 40.2% reported that they smoke out of spite. Students reported that their parents are aware that their offspring smoke in a proportion of 36.7%. Social standards and parental example were found to be the main determinants for starting smoking. The majority of the students (95.2%) stated that they are aware of the hazards associated with smoking. Discussion: Our findings highlight the need for smoking control interventions aimed at young people. Smoking is a major, yet preventable cause of morbidity and mortality. For these reasons, we view that adolescents should be targeted with a well-planned integrated anti-smoking policy and not just an initiative for raising awareness of smoking hazards.

High Dose Therapy with Autologous Stem Cell Transplantation for Solitary Bone Plasmacytoma Complicated by Local Relapse or Isolated Distant Recurrence

We report three patients with solitary bone plasmacytoma (SBP) who developed either local recurrence within the radiotherapy field or an isolated distal recurrence and who were treated with high dose therapy supported by autologous stem cell transplantation. All patients remain without evidence of disease for 4-10 years after the procedure. High dose therapy may be of value and require further study in patients with SBP who develop local or distant failure.

Lowering of furosemide dosage after clinical stabilization in patients with congestive heart failure

Objectives — This study was performed to examine the safety of reducing the long-term doses of furosemide administered to patients with congestive heart failure (CHF) stabilized on a standard medical treatment. Methods and results — Twenty-nine patients with advanced CHF were treated with enalapril, digoxin, nitrates, and furosemide, as needed to alleviate their symptoms, and remained clinically stable for at least 3 months on those doses. Subsequently, the daily dose of furosemide was reduced to 1/3 of the previous dose, while the concomitant therapy was unchanged. All patients underwent a thorough clinical evaluation and right-heart catheterization before and 2 months after the furosemide dose reduction. After the treatment optimization the NYHA functional class decreased from 2.3±0.6 to 1.4±0.6 (p = 0.000), and the left ventricular ejection fraction increased from 22±10% to 32±13%, (p = 0.000). Clinical and haemodynamic evaluation before and after 2 months of treatment with lower furosemide doses showed that 24 of the 29 patients (83%) remained in a stable NYHA functional class and maintained a stable haemodynamic status. In the remaining 5 patients (17%), mean NYHA functional class increased from 1.8±0.4 to 2.4±0.6 (p = 0.07), accompanied by a significant increase of the right and left ventricular filling pressures from 4.2±2.7 to 9.0±3.0 mm Hg, p = 0.018 and from 8.6±3.0 to 19.8±3.6 mm Hg, p = 0.017, respectively. These 5 patients returned to a stable clinical status upon resumption of the prior doses of furosemide. Conclusions — Most patients with chronic CHF who were clinically stabilized on high doses of furosemide remained stable on a maintenance dose equal to one-third of the dose needed for their stabilization. Patients unable to tolerate the dose reduction regained their previous clinical status following the resumption of the prior diuretic doses.

Effect of Combined Treatment Methods on Quality of Life in Patients With Pancreatic Cancer

We aimed to analyze the effect of combined treatment methods on quality of life (QoL) in patients diagnosed with pancreatic cancer. Therefore, we prospectively analyzed 30 patients with unresectable, without distant metastases, pancreatic cancer. Patients were randomized to 1 of 2 treatment arms: radiotherapy with 5-fluorouracil or radiotherapy with gemcitabine. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire in both treatment groups. QoL was evaluated before and after treatment. We found that that both concomitant chemoradiation methods have similar impact on QoL in patients with unresectable pancreatic cancer.

The role of paroxetine in fatigue and depression of patients under chemotherapeutic treatment.

We evaluated paroxetine for the treatment of fatigue and depression in patients with solid tumors after chemotherapy, and we found that paroxetine is effective for the treatment of depression during chemotherapy but has no benefit for the treatment of fatigue.

Efficacy and safety of capecitabine and oxaliplatin combination as second-line treatment in advanced colorectal cancer.

The aim of this study was to determine the efficacy and safety of administering a combination of capecitabine and oxaliplatin in patients with advanced colorectal cancer, resistant to leucovorin/5-fluorouracil and irinotecan. Fifty-four patients with advanced colorectal cancer were prospectively evaluated (mean age 63 years, male/female 2:1) who had been previously treated with schemes containing fluoropyrimidines and irinotecan. All patients received oxaliplatin (130 mg/m2 as 2-hour intravenous infusion) the first day of the cycle and capecitabine (1000 mg/m2) twice daily, days 1-14. Cycles were repeated every 21 days until either disease progression or unacceptable toxicity. Patients were evaluated regarding their response to treatment every 9 weeks (toxicity was evaluated every 3 weeks). Total response rate was 28.3%. Median total survival was 13.5 months, and median time to progression was 5.3 months in a follow up of 24 months. Major adverse events were neutropenia, nausea, diarrhea, hand/foot syndrome, and neurotoxicity. No treatment-related or grade 4 toxicity-related deaths were observed. Additionally, no dosage decrease was required, and only 4 cycles were withheld for 1 week because of neutropenia. The combination of oxaliplatin and capecitabine is efficient and safe for patients with advanced colorectal cancer who have been previously treated with other therapeutic schemes. Furthermore, this is a convenient and well-tolerated scheme.