Feasibility and safety of a modified outpatient regimen with intravenous/intraperitoneal chemotherapy for optimally debulked stage III ovarian cancer.

OBJECTIVE: Intraperitoneal (i.p.) chemotherapy improves survival in optimally debulked ovarian cancer patients. However, the need for inpatient administration and the perceived higher toxicity rates compared with standard intravenous chemotherapy have limited its widespread application. Several modified outpatient schemes, such as the Spanish Ovarian Cancer Research Group (GEICO) regimen, have been tested and have reported overall better tolerance with an improvement in completion treatment rates. The aim of our study was to assess the toxicity of the GEICO regimen in patients treated at our institution. METHODS: We reviewed clinical records of stage III ovarian cancer patients with optimally debulked primary cytoreduction surgery that were treated from June 2009 to April 2013 with the GEICO regimen. Patients received intravenous paclitaxel (175 mg/m2) for 3 hours on day 1, i.p. cisplatin (100 mg/m2) on day 2, and i.p. paclitaxel (60 mg/m2) on day 8 every 21 days for a maximum of 6 cycles. RESULTS: Twenty-one patients were identified. In 67% of the patients, i.p. port placement was performed at the primary surgery. The most common grade 3-to-4 toxicities seen were abdominal pain (14.3%) and neurotoxicity (9.5%). Eighteen patients (85.7%) completed the 6 cycles. Three patients stopped chemotherapy because of treatment-related toxicity. There were no serious port-related complications. With a median follow-up of 46 months, median progression-free survival was 23 months (95% confidence interval [11.8-34.6]). Nine patients (42.9%) have relapsed; most relapses were multifocal and extraperitoneal. CONCLUSION: The administration of the GEICO outpatient modified regimen was feasible with a good safety profile. It seems to show less toxicity than previously reported IP chemotherapy regimens. In our institution, port-related complications were infrequent and easily managed. However, further studies are warranted to establish the optimal i.p. regimen in a prospective manner and to validate it in a larger phase 3 trial.

SNPs and taxane toxicity in breast cancer patients.

AIM: In order to identify genetic variants associated with taxanes toxicity, a panel with 47 SNPs in 20 genes involved in taxane pathways was designed. PATIENTS & METHODS: Genomic DNA of 113 breast cancer patients was analyzed (70 taking docetaxel, 43 taking paclitaxel). RESULTS: Two SNPs associated with docetaxel toxicity were identified: CYP3A4*1B with infusion-related reactions; and ERCC1 Gln504Lys with mucositis (p≤0.01). Regarding paclitaxel toxicity: CYP2C8 HapC and CYP2C8 rs1934951 were associated with anemia; and ERCC1 Gln504Lys with neuropathy (p≤0.01). CONCLUSION: Genes involved in DNA repair mechanisms and reactive oxygen species levels influence taxane toxicity in cancer patients treated with chemotherapy schemes not containing platinum. These findings could lead to better treatment selection for breast cancer patients.

Advantages of one step nucleic acid amplification (OSNA) whole node assay in sentinel lymph node (SLN) analysis in breast cancer.

BACKGROUND: The purpose of this study is to present our first results of sentinel node analysis (SLN) by one step nucleic acid amplification (OSNA) in routine clinical practice in our centre and compare them with the results of classic histopathological analysis in a historical cohort from our same institution. METHODS: 407 patients (total study population) with early breast cancer and no clinical nodal involvement underwent SLN biopsy in our institution. The SLN was analysed by OSNA in 164 biopsies. OSNA results were compared with the conventional histopathology study of 244 patients who had undergone SLN biopsy previously. The characteristics of the patients in both groups were evaluated and a comparison was made of the rate of metastases detected by both methods and of the surgical procedures needed in each group. We also investigated the state of non-sentinel lymph nodes if micrometastases where found in SLN. RESULTS: SLN biopsy result was considered as positive in 45 patients (28%) in the OSNA group and in 58 in the historical group (24%). There was no difference in the rate of macrometastases (16,5% for OSNA, 20% for HE) but we found differences in the rate of micrometastases (11% for OSNA and 3,6% for HE p = 0.0007). Axillary lymphadenectomy (ALND) was performed in 43/45 cases in the OSNA group and in 51/58 of the historical group. In all patients diagnosed by OSNA, ALND was performed during the initial surgical procedure. In the historical cohort ALND was performed during the initial surgical procedure in 41 patients and in a second surgical procedure in 10 patients. Patients from both groups with micrometastases in the SLN had no metastases in other nodes when the ALND was performed. CONCLUSIONS: OSNA analysis allows the detection of SLN metastases as precisely as conventional pathology with an increased detection of micrometastases. The OSNA method can reduce the need of a deferred lymphadenectomy.

Long-term results of neoadjuvant chemotherapy and combined chemoradiotherapy before surgery in the management of locally advanced oesophageal cancer: a single-centre experience.

INTRODUCTION: Neoadjuvant chemoradiotherapy before surgery is an option in the treatment of locally advanced resectable oesophageal cancer (EC). However toxicity is substantial and the improvement in overall survival (OS) with this approach is controversial. METHODS: This was a prospective, single-centre study of neoadjuvant chemotherapy and concomitant chemoradiotherapy with CDDP and 5-FU and 50.4 Gy of external radiotherapy before possible radical surgery in patients with locally advanced resectable EC. If surgery was not possible, a second-phase radiotherapy boost of 10 Gy and one cycle of modified dose chemotherapy were used. RESULTS: Seventy-three patients included between 1998 and 2007: 96% males, median age 61, 83% squamous cell carcinomas, 23% lower third tumours, 36% stage II and 54% stage III and 47% local lymph node involvement. Eighty-six percent completed the combined protocol. Main grade 3-4 toxicities: mucositis (19%) and infections (8%); 4 toxic deaths. Clinical response rates: complete response 54%, partial response 27%, stable disease 8%. Twenty-five patients proceeded to surgery, with radical resection in 24. Pathological response rate: complete response 32%, partial response 52%, progression 16%. There were 7 postoperative deaths and 16 of 34 patients that did not have surgery received the second-phase RT boost. Survival analysis: Median follow-up of 64 months (range 6-134 months). Median OS of 10.33 months. 2-year and 5-year OS of 22 and 16%. The only significant prognostic factor in OS is the clinical complete response rate: 13.9 vs. 7.7 months (p=0.0049). CONCLUSIONS: Our protocol offers a high rate of clinical activity although it is relatively toxic and seems to increase the postoperative mortality, which would blunt any small improvement in survival. The achievement of a complete response is a powerful prognostic factor.