Andreas du Bois

Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery in patients with operable breast cancer. However, uncertainty remains regarding surgical procedures and predictors for successful breast-conserving surgery. This study was an analysis of surgical data of a representative data subset of 607 patients enrolled in the GEPARDUO study. This prospective, multicenter, phase III study randomly assigned patients with operable breast cancer (≥ 2 cm) to neoadjuvant 8-week dose-dense doxorubicin plus docetaxel or a 24-week schedule of doxorubicin plus cyclophosphamide followed by docetaxel (AC-DOC). Breast conservation was attempted in 493 (81.2%) patients, but 43 patients eventually required mastectomy, thus resulting in a breast-conserving surgery rate of 74.1%. Breast-conserving re-excision was performed in 61 patients (12.4%). Factors associated with a significantly higher breast-conserving surgery rate were a prechemotherapy tumor size ≤ 40 mm, nonlobular histological characteristics, treatment with AC-DOC, clinical response, postchemotherapy tumor size ≤ 20 mm, and treatment in a larger center (>10 enrolled patients). Nonlobular histological characteristics and intraoperative frozen-section analysis for margin evaluation were associated with significantly lower reoperation rates (P = .015). Breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer. For surgical planning, tumor characteristics and response to neoadjuvant chemotherapy should be taken into account. Improved breast-imaging modalities are necessary to improve detection of residual disease after neoadjuvant chemotherapy, especially when breast cancer is of lobular invasive histology. Margin assessment by intraoperative frozen-section analysis is helpful to avoid reoperation. To achieve an optimal result, an interdisciplinary surgical approach is important.

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.

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2).

Background: Single-agent platinum and single-agent pegylated liposomal doxorubicin (PLD) are both effective in the treatment of gynecologic malignancies. Based on evidence that combination platinum-containing regimens offer superior efficacy versus single-agent regimens, we conducted this study to determine the maximum tolerated dose (MTD) of PLD in combination with carboplatin. Patients and methods: In this phase I/II dose-finding study, six courses of PLD (20, 30, 40 or 50 mg/m²) and carboplatin (AUC 6) were administered every 28 days to women with advanced gynecologic malignancies. Three to six patients were treated at each dose level; an additional 12 patients were treated at the MTD. Results: PLD 40 mg/m² was identified as the MTD when administered with carboplatin. Five of 18 patients experienced a dose-limiting toxicity at the MTD; two patients had grade 3/4 neutropenia, and one each had grade 3 emesis and grade 3 thrombocytopenia and thrombosis. No patient developed cardiotoxicity. In 11 patients evaluable for response, there were two complete responses, two partial responses and four patients with stable disease. Conclusions: The MTD for PLD when administered in combination with carboplatin is 40 mg/m². This regimen is well tolerated and offers promising activity in women with advanced gynecologic malignancies.

Gynecological Cancer Intergroup (GCIG) and its member organizations: 1AGO-OVAR (Germany), 2ANZGOG (Australia – New Zealand), 4EORTC (Europe), 6GEICO (Spain), 9GINECO (France), 3GOG (USA), 8JGOG (Japan), 10MRC/NCRI (UK), 7NCIC-CTG (Canada), 15NCI-US (USA), 5NSGO (Scandinavia), 12RTOG (USA), 11SGCTG (Scotland), and with representation of 14IGCS and 13the organizational team of the two prior International OCCC

Ziel: Analyse der Versorgungsstruktur und Qualität der Therapie des Ovarialkarzinoms in Deutschland. Untersuchung inwieweit die Therapieleitlinien umgesetzt werden, sowie Beschreibung von Prognosefaktoren. Methode: 2. nationale Erhebung der Patientinnen mit histologisch gesichertem epithelialen Ovarialkarzinom mit Diagnose im 3. Quartal 2001. Beschreibung der operativen und systemischen Therapie beim frühen (FIGO I-IIA) und fortgeschrittenen Ovarialkarzinom (FIGO IIB-IV). Univariate und multivariate Analyse von Prognosefaktoren. Ergebnisse: Mit 476 Patientinnen wurden mehr als ein Drittel aller in Q III in Deutschland diagnostizierten Ovarialkarzinome analysiert. Beim frühen Ovarialkarzinom erhielten nur 35,5 % der Patientinnen eine Behandlung gemäß den deutschen Therapieleitlinien. Beim fortgeschrittenen Karzinom konnte bei 61,4 % der Tumor komplett oder bis auf maximal 1 cm durchmessende Reste reseziert werden. Die empfohlenen Platin-Paclitaxel-Chemotherapie erhielten etwa ³/₄ aller Patientinnen mit Stadium FIGO IIB-IV. In der multivariaten Analyse waren fortgeschrittenes Stadium, schlechter Allgemeinzustand, Co-Morbidität, Alter über 65 Jahre, Aszites, postoperativer Tumorrest und eine Therapie unter Standardniveau signifikant mit schlechteren Überlebenschancen assoziiert. Schlussfolgerung: Die Umsetzung der Therapieleitlinien in Deutschland unterliegt einer erheblichen Heterogenität und ist insgesamt zu gering. Diese Analyse zeigt Felder auf, in denen Verbesserungen möglich, aber auch dringend erforderlich sind. Purpose: To evaluate pattern and quality of care for ovarian cancer in Germany and analyze adherence to treatment guidelines as well as prognostic factors for survival. Methods: Nationwide survey including patients with histological proven invasive epithelial ovarian cancer diagnosed in the third quarter 2001 including descriptive analysis of pattern of surgical care and systemic treatment in early (FIGO I-IIA) and advanced (FIGO IIB-IV) ovarian cancer and both univariate and multivariate analysis of prognostic factors. Results: 476, representing more than one third of all patients diagnosed in Q III 2001 in Germany were included. Standard care according to German guidelines was provided to only 35.5 % of patients with early ovarian cancer. Optimal debulking was reported for 61.4 % patients with FIGO stages IIB-IV. Recommended platinum-paclitaxel chemotherapy was given to 3 out of 4 patients in advanced disease. Multivariate analysis showed advanced stage, poor performance status, co-morbidity, ascites, postoperative tumor residuals, and less than standard care to be associated with inferior survival. Conclusions: Adherence to treatment guidelines showed remarkable variety among German hospitals indicating options and need for improvement.