Impact of FDG PET-CT imaging on the decision making in the biologic suspicion of ovarian carcinoma recurrence.

OBJECTIVES: The aim of this prospective study was to evaluate the impact of integrated PET-CT on treatment management in ovarian carcinoma recurrence suspicion because of increased CA-125. METHODS: Twenty-nine patients (mean age=61 years), initially treated for ovarian carcinoma (FIGO stage I n=2, stage II n=3, stage III n=21 and stage IV n=3), presenting with increased CA-125 (mean=160 IU/ml, range 33-1930), underwent subsequently a CT and a PET-CT scans. The recurrence was acknowledged by the referring physicians for all patients. The impact of PET-CT on patient's management was evaluated by comparing the therapeutic decision mentioned respectively on the pre and post PET-CT questionnaires filled in by the oncologists. RESULTS: The CT scan was positive in 22/29 patients (76%) and negative in 7/29 patients (24%). The PET-CT scan was positive in 27/29 patients (93%) and negative in 2/29 (7%) patients. Five out of the seven patients with a negative CT scan had a positive PET-CT scan. In comparison to CT scan alone, the PET-CT scan modified the disease distribution for 16 patients (55%; p<0.001) in the following ways: more advanced disease (n=11), more limited disease (n=4), and different localizations (n=1). The assessment of pre and post PET-CT questionnaires showed a statistically significant change in the decision making for 10 patients (34%, p<0.0001). CONCLUSION: This questionnaire-based study showed that PET-CT imaging allows a better restaging than CT and induces a change in clinical management in over one third of patients with suspected ovarian carcinoma recurrence on increased CA-125.

Brain metastases from breast carcinoma: validation of the radiation therapy oncology group recursive partitioning analysis classification and proposition of a new prognostic score.

PURPOSE: To validate the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification and determine independent prognostic factors, to create a simple and specific prognostic score for patients with brain metastases (BM) from breast carcinoma treated with whole-brain radiotherapy (WBRT). METHODS AND MATERIALS: From January 1998 through December 2003, 132 patients with BM from breast carcinoma were treated with WBRT. We analyzed several potential predictors of survival after WBRT: age, Karnofsky performance status, RTOG-RPA class, number of BM, presence and site of other systemic metastases, interval between primary tumor and BM, tumor hormone receptor (HR) status, lymphocyte count, and HER-2 overexpression. RESULTS: A total of 117 patients received exclusive WBRT and were analyzed. Median survival with BM was 5 months. One-year and 2-year survival rates were 27.6% (95% confidence interval [CI] 19.9-36.8%) and 12% (95% CI 6.5-21.2%), respectively. In multivariate analysis, RTOG RPA Class III, lymphopenia (< or =0.7 x 10(9)/L) and HR negative status were independent prognostic factors for poor survival. We constructed a three-factor prognostic scoring system that predicts 6-month and 1-year rates of overall survival in the range of 76.1-29.5% (p = 0.00033) and 60.9-15.9% (p = 0.0011), respectively, with median survival of 15 months, 5 months, or 3 months for patients with none, one, or more than one adverse prognostic factor(s), respectively. CONCLUSIONS: This study confirms the prognostic value of the RTOG RPA classification, lymphopenia, and tumor HR status, which can be used to form a prognostic score for patients with BM from breast carcinoma.

Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens.

PURPOSE: Despite the progress that has been achieved, long-term survival rates in patients with advanced ovarian cancer are still disappointing. One attempt to improve results could be the addition of non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines were among the candidates for incorporation as a third drug into first-line regimens. PATIENTS AND METHODS: We performed a prospectively randomized phase III study comparing carboplatin-paclitaxel (TC; area under the curve 5/175 mg/m2, respectively) with epirubicin 60 mg/m2 added to the same combination (TEC) in previously untreated patients with advanced epithelial ovarian cancer. All drugs were administered intravenously on day 1 of a 3-week schedule for a planned minimum of six courses. RESULTS: Between November 1997 and February 2000, 1,282 patients were randomly assigned to receive either TC (635 patients) or TEC (647 patients), respectively. Grade 3/4 hematologic and some nonhematologic toxicities (nausea/emesis, mucositis, and infections) occurred significantly more frequently in the TEC arm. Accordingly, quality-of-life analysis showed inferiority of TEC versus TC. Median progression-free survival time was 18.4 months for the TEC arm and 17.9 months for the TC arm (hazard ratio [HR], 0.95; 95% CI, 0.83 to 1.07; P = .3342). Median overall survival time was 45.8 months for the TEC arm and 41.0 months for the TC arm (HR, 0.93; 95% CI, 0.81 to 1.08; P = .3652). Similar nonsignificant differences were observed when strata were analyzed separately. CONCLUSION: Addition of epirubicin to TC did not improve survival or time to treatment failure in patients with advanced epithelial ovarian cancer; therefore, it cannot be recommended for clinical use in this population.

Pharmacokinetic linearity of i.v. vinorelbine from an intra-patient dose escalation study design.

As pharmacokinetics represents a bridge between pharmacological concentrations and clinical regimens, the pharmacokinetic exploration of the therapeutic dose range is a major outcome. This study was aimed at assessing pharmacokinetic linearity of i.v. vinorelbine through an open design with intra-patient dose escalation (3 doses/group). Three groups of six patients received either 20-25-30 mg/m2; or 25-30-35 mg/m2; or 30-35-40 mg/m2. The inclusion criteria were: histologically confirmed tumour with at least one assessable target lesion, age 25-75 years, WHO PS < or =2, normal haematology and biochemistry, life expectancy > or =3 months. The pharmacokinetics was evaluated in both whole blood and plasma over 120 h. Twenty-six patients were recruited and 18 were evaluable for pharmacokinetics. The toxicity consisted in grade < or =3 leucopenia and neutropenia (<20% of courses) and two grade 4 constipation with rapid recovery (2/54 courses). Compared to blood, plasma was demonstrated to underestimate the pharmacokinetic parameters. In blood, the drug total clearance was about 0.6 l/h/kg, with minor contribution of renal clearance, steady state volume of distribution close to 13 l/h/kg, and elimination half-life at about 40 h. A pharmacokinetic linearity was demonstrated up to 40 mg/m2, and even up to 45 mg/m2 when pooling data from another study. A pharmacokinetic-pharmacodynamic relationship was evidenced on leucopenia and neutropenia when pooling the data from the two studies.

Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01).

PURPOSE: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done. RESULTS: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively. CONCLUSION: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.

Individual adaptive dosing of topotecan in ovarian cancer.

PURPOSE: To take into account relationships between topotecan area under the plasma concentration (AUC) versus time curve and percentage decrease of neutrophil count previously shown when topotecan is administered on a 5-day, daily schedule. A multicentric clinical trial with individualized dosing of topotecan was performed in patients with platinum-refractory ovarian cancer. The primary goal of this study was to evaluate the toxicity of topotecan when the interindividual variability in plasma drug exposure is decreased. EXPERIMENTAL DESIGN: A total of 39 patients were evaluable. In cycle 1, the daily dose for the last 2 days was dependent on the observed topotecan AUC at day 1; the general objective was to constrain the overall AUC (i.e., from day 1 to day 5) within 37,500-75,000 nM.min. A pharmacokinetic study was also performed on day 5 of cycle 1 and day 1 of cycle 2 to evaluate the intrapatient pharmacokinetic variability both within cycle 1 and between cycles. RESULTS: The dose of topotecan was decreased for 20 patients and increased for only 1 patient within cycle 1. The total administered dose was correlated to the creatinine clearance. The dose adjustments allowed control of the topotecan exposure: mean (+/-SD) observed AUC of 70,697 (+/-12,364) nM.min. Fourteen cases of dose-limiting toxicity were observed, mainly in patients who previously received two different regimens of chemotherapy without a washout period before topotecan treatment. An overall response rate of 21% was observed in the 33 patients evaluable. CONCLUSION: Dose adjustments are required not only in patients with creatinine clearance below 40 ml/min, but also in those with values between 40 and 60 ml/min (recommended starting dose is 1.2 mg/m(2)). By performing drug monitoring and taking into consideration the past treatment of each patient, better dose individualization can be obtained.