Association of pegylated liposomal doxorubicin and ifosfamide in early recurrent ovarian cancer patients: a multicenter phase II trial.

OBJECTIVE: To evaluate the efficacy of pegylated liposomal doxorubicin (PLD) and continuous infusion ifosfamide (IFO) in ovarian cancer patients who relapse within 1 year after first-line paclitaxel-platinum-based chemotherapy. METHODS: Patients were stratified according to treatment-free interval (TFI) (or=6 months). PLD (40 mg/m(2), day 1), IFO (1700 mg/m(2), infusion days 1-3), and mesna were given every 28 days for 6-9 cycles. Primary endpoint was objective response rate (ORR). Secondary endpoints were response duration, progression free survival (PFS), overall survival (OS), and toxicity. RESULTS: There were 98 evaluable patients (58%, TFI<6 months). Median number of cycles was 5 (range: 1-9). The frequency of grade 3/4 anemia, thrombocytopenia, and neutropenia was 7%, 3%, and 48%, respectively; febrile neutropenia was 3%. A low rate of grade 3/4 non-hematologic toxicities was reported, including nausea/vomiting (3/4%), hand-foot syndrome (2%), and mucositis (2%). The ORR was 28% (41% and 19% in patients with TFI >or=6, or <6 months, respectively); rate of disease stabilization was 26%; response duration and median OS were 6 (2.4-26) and 14 (1-46) months, respectively. CONCLUSION: The combination of PLD and continuous IFO is a feasible and efficient treatment in patients with relapsed ovarian cancer, especially with TFI between 6 and 12 months. This regimen may represent an alternative to platinum reintroduction and should be evaluated in a randomized trial.

[Hairy cell leukemia: therapeutic approaches]. / La leucémie à tricholeucocytes: approches thérapeutiques.

Hairy cell leukemia is a rare lymphoproliferative B disorder. It usually occurs in men older than 50 years. Until 1984, therapeutic approaches had been disappointing and most of the patients died from complications of cytopenia. The introduction of interferon and, more recently of purine analogues (pentostatine and 2-chlorodeoxyadenosine) improved outcome of this disease. Nevertheless, if complete remissions may be achieved sometimes with interferon and more frequently with purine analogues, none of these treatments seems able to remove hairy cells. So, therapeutic decision has to be made according to the efficacy and the potential adverse effects of these drugs.

[Yersinia enterocolitica septicemia, iron overload and deferoxamine]. / Septicémie à Yersinia enterocolitica, surcharge ferrique et déféroxamine.

Infections due to Yersinia enterocolitica are usually limited to the bowel. When infection is generalized, the role of iron overload and iron chelation has been discussed. We report the case of a 55 year-old patient with sideroblastic anemia who received repetitive transfusions and deferoxamine for 4 years and heme arginate for 2 months, and who was admitted in our institution for Yersinia enterocolitica sepsis. Treatment by third-generation cephalosporins and aminoglycosides has allowed favorable outcome.

[Acute drug-induced agranulocytosis. Clinical study apropos of 30 patients and evolution of etiologies over 2 decades]. / Agranulocytoses aiguës médicamenteuses. Etude clinique à propos de 30 patients et évolution des étiologies sur 2 décennies.

Between 1982 and 1993, 30 patients were treated for drug-induced agranulocytosis. They did not receive cytotoxic chemotherapy nor radiotherapy during the past 6 months. There is a higher incidence in women (21 females, nine males). Mean age is 59.3 years old. The drug could be found in 25 cases including noramidopyrine five cases, antithyroid drugs four cases, non steroidal anti-inflammatories drugs four cases. Five patients died of infection during agrulocytosis. Sepsis was documented in three cases. We used hematopoietic growth factors in two cases. Neutrophils rose up to 0.5.10(9)/l between 2 to 14 days after the diagnosis and 1.10(9)/l between 3 to 16 days. Time when absolute neutrophil count was less than 0.5.10(9)/l was shorter (p = 0.008) when bone marrow was rich with maturation arrest but with few or no mature forms rather than reduction of granulocytic precursors. By comparison with a similar study made in the same institution between 1971 and 1981, there were fewer cases each year. Drugs involved were not similar: phenicols were not found, reference to noramidopyrine is less frequent. Now antithyroid drugs is becoming one of the most important etiologies.

First-line simplified GEMOX (S-GemOx) versus classical GEMOX in metastatic pancreatic cancer (MPA): results of a GERCOR randomized phase II study.

PURPOSE: GemOx was defined as a D1-D2 schedule, based on preclinical data. In order to improve convenience for patients, we evaluated a simplified D1-D1 GemOx regimen (S-GemOx) in MPA. PATIENTS AND METHODS: Patients (pts) with MPA were 2:1 randomly assigned for first-line treatment to S-GemOx (gemcitabine 1,000 mg/m(2), 100-minute infusion D1 immediately followed by oxaliplatin 100 mg/m(2), 120-minute infusion) or to GemOx (Gem D1 and ox D2). Treatment was repeated in each arm every 2 weeks until disease progression. Stratification was performed on center and PS. RESULTS: Fifty-seven pts were enrolled, S-GemOx = 37 (PS 2: 22%), GemOx = 20 (PS 2: 20%). Populations were well balanced for age (64.9 vs 66.6 years); gender (57 vs 65% male), location of primary tumor (pancreas head: 49 vs 50%), and metastatic sites (liver 76 vs 85%; peritoneum 24 vs 20%; lung 16 vs 10%; lymph nodes 14 vs 15%; other 5 vs 5%). Tumor differentiation significantly differed between the 2 groups (S-GemOx: 8% poorly differentiated vs GemOx: 36%). Response rate was 27% (95% CI: 12-42) in arm S-GemOx and 10% (95% CI: 0-23) in GemOx. Median PFS was 4.0 and 2.5 months in S-GemOx and GemOx, respectively. Median OS was 7.6 and 3.2 months in S-GemOx and GemOx, respectively. Since more cycles were administered in S-GemOx (8.5 [1-29] vs 5.8 [2-12]), grade 3 oxaliplatin-induced neuropathy was higher in S-GemOx [21.6 vs 0%]). CONCLUSIONS: Activity and tolerance of S-GemOx are in the same range as compared to our previous experiences of classical GemOx in metastatic pancreatic cancer. The very bad outcome of patients randomized in GemOx arm could at least be in part explained by the high-rate of poorly differentiated tumors.