Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial.

BACKGROUND: The primary aim of this trial was to determine the recommended phase II dose (RP2D) of weekly paclitaxel (wP) administered in combination with oral metronomic cyclophosphamide (OMC). METHODS: Patients ≥ 18 years of age with refractory metastatic cancers were eligible if no standard curative measures existed. Paclitaxel was administered IV weekly (D1, D8, D15; D1 = D28) in combination with a fixed dose of OMC (50 mg twice a day). A 3 + 3 design was used for dose escalation of wP (40 to 75 mg/m2) followed by an expansion cohort at RP2D. Dose-limiting toxicity (DLT) was defined over the first 28-day cycle as grade ≥ 3 non-hematological or grade 4 hematological toxicity (NCI-CTCAE v4.0) or any toxicity leading to a dose reduction. RESULTS: In total, 28 pts. (18 in dose-escalation phase and 10 in expansion cohort) were included, and 16/18 pts. enrolled in the dose-escalation phase were evaluable for DLT. DLT occurred in 0/3, 1/6 (neuropathy), 0/3 and 2/4 pts. (hematological toxicity) at doses of 40, 60, 70 and 75 mg/m2 of wP, respectively. The RP2D of wP was 70 mg/m2; 1/10 patients in the expansion phase had a hematological DLT. At RP2D (n = 14), the maximal grade of drug-related adverse event was Gr1 in three patients, Gr2 in six patients, Gr3 in one patient and Gr4 in one patient (no AE in three patients). At RP2D, a partial response was observed in one patient with lung adenocarcinoma. CONCLUSION: The combination of OMC and wP resulted in an acceptable safety profile, warranting further clinical evaluation. TRIAL REGISTRATION: TRN: NCT01374620 ; date of registration: 16 June 2011.

Managing Endometrial Cancer: The Role of Pelvic Lymphadenectomy and Secondary Surgery.

PURPOSE: In November 2010, the French National Cancer Institute published new guidelines for managing endometrial cancer. Pelvic lymphadenectomy is not indicated for preoperative low-intermediate risk type 1 endometrial cancer, and high-risk patients should undergo secondary surgery with para-aortic lymphadenectomy. This study evaluated these new guidelines with regard to overall survival (OS), relapse-free survival (RFS), and morbidity for patients with low-intermediate risk disease. METHODS: We evaluated all type 1 endometrial cancer patients with low-intermediate risk of recurrence who were treated from 1 January 1997 through 31 December 2012. All patients were classified according to the 2009 International Federation of Gynecology and Obstetrics staging criteria and the European Society for Medical Oncology. RESULTS: Overall, 230 patients were included (159 before and 71 after the new guidelines were issued). Pelvic lymphadenectomies were performed before and after the new guidelines in 77.4 and 28.6 % of patients, respectively (p < 0.001). After 2010, eight patients also underwent secondary surgery, which consisted of a para-aortic lymphadenectomy for lymphovascular space invasion (LVSI). This second surgery changed the adjuvant treatment for one patient. OS and RFS were similar between both groups, and no difference in morbidity was observed between the groups. LVSI was an independent factor for OS [hazard ratio (HR) 7.2, 95 % CI 3.1-17; p < 0.001] and RFS (HR 3.7, 95 % CI 1.6-8.5; p < 0.003). CONCLUSIONS: Fewer pelvic lymphadenectomies in low-intermediate risk patients did not affect OS, RFS, or morbidity, including patients with secondary surgery. We must gather additional data with a longer follow-up period to not only confirm our results but to also fully investigate the paradoxical absence of decreased morbidity that our study has shown.

Chemotherapy drug extravasation in totally implantable venous access port systems: how effective is early surgical lavage?

PURPOSE: Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL). METHODS: Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively. RESULTS: Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft. CONCLUSIONS: CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.