Cycles Of Paclitaxel Research Articles

Empty hemiscrotum and a giant abdominal mass case report

Testicular germ cell tumors are the most common adult male malignancy among men 20–35 years, having a favorable prognosis when detected at early stages. Testicular teratomas are derived from embryonic tissue within gonads and tend to exhibit locally invasive and chemo resistant behavior. Cryptorchidism is a significant risk factor for the development of testicular germ cell tumors, therefore, patients with undescended testicles should be closely monitored. Pre-pubertal orchiopexy should be considered to reduce the risk of germ cell tumors and improve its early detection. We report a 26-year-old male with an empty hemiscrotum who incidentally presented with a large intraabdominal mass after being evaluated for a broken jaw. He was lost to follow-up and re-presented with a 19 cm intraabdominal mass and alpha-fetoprotein of 5,310 ng/mL, beta-human chorionic gonadotrophin of 0.5 MIU/mL, and a lactate dehydrogenase of 846 U/L. After completion of four cycles of paclitaxel, ifosfamide, and cisplatin chemotherapy, he underwent a left orchiectomy, bilateral full template retroperitoneal lymph node dissection, and a partial cystectomy. Final pathology revealed a malignant mixed germ cell tumor consisting of 75% immature teratoma, 25% mature teratoma, and involvement in zero of twenty-three retroperitoneal lymph nodes. The patient recovered well with no signs of recurrence. This case highlights the importance of proper genitourinary assessment during routine physical examinations and close follow-up of adult patients with cryptorchidism.

Less nephrotoxicity of paclitaxel and ifosfamide plus nedaplatin for refractory or relapsed germ cell tumors in patients with impaired renal function.

To determine the safety and efficacy of the combined regimen of paclitaxel and ifosfamide plus nedaplatin for patients with refractory or relapsed germ cell tumors and impaired renal function. Of a total of 68 patients who received paclitaxel, ifosfamide and nedaplatin chemotherapy for germ cell tumors, those with an estimated glomerular filtration rate <60mL/min/1.73m2 before paclitaxel, ifosfamide and nedaplatin treatment were defined as having renal dysfunction. The combination chemotherapy regimen included paclitaxel (210mg/m2 on day1) and ifosfamide (1.2g/m2 on days2-6) with nedaplatin (100mg/m2 on day2) on a 3-week cycle. A total of 10 patients had renal dysfunction with a median estimated glomerular filtration rate of 49.97mg/mL/1.73m2 (range 31.7-57.5mg/mL/1.73m2 ). Paclitaxel, ifosfamide and nedaplatin chemotherapy was given as second-line therapy in four patients, third-line in four and fourth-line or later in two. Patients with impaired renal function received pretreatment of a median of 5.5 cycles of platinum-based chemotherapy (range 3-11 cycles) with a median cisplatin dose of 550mg/m2 . The patients were given two to six cycles of paclitaxel, ifosfamide and nedaplatin chemotherapy with no dose reduction, with an overall response rate of 60%. Chemotherapy-induced kidney dysfunction was not observed in any patient with decreased renal function. Furthermore, there was no difference in the frequency of adverse events between patients with renal dysfunction (estimated glomerular filtration rate <60mL/min/1.73m2 ) and those with normal renal function (estimated glomerular filtration rate ≥60mL/min/1.73m2 ). Paclitaxel, ifosfamide and nedaplatin chemotherapy can be considered a safe and effective regimen that results in less nephrotoxicity in germ cell tumor patients with renal dysfunction.

LBA8_PR - KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC)

LBA8_PR - KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC)

1273P - Durvalumab and paclitaxel combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy

BackgroundImmunotherapy with anti PD-1/PD-L1 antibodies as a monotherapy showed promising results with limited success in triple negative breast cancer. As the combination of paclitaxel and anti PD-L1 was likely synergistic, our aim was to test safety, toxicities, tolerability and efficacy of this combination. MethodsWe have initiated an open label, interventional phase I/II clinical trial to test the safety and efficacy of a combination of Durvalumab (therapeutic anti-PD-L1 antibody) and paclitaxel for the treatment of metastatic triple negative breast cancer (TNBC). After 1 cycle of weekly paclitaxel alone, Durvalumab was given every two weeks in combination with paclitaxel that was delivered on days 1, 8 and 15 of each 28 days’ cycle. ResultsBetween 2017-2019, we enrolled 19 patients (25-61 years old) of which 14 were treated with the combination therapy, while the remaining 5 dropped out due to tumor progression (n=3) or intolerance to first cycle of paclitaxel alone (n=2). Patients had metastatic infiltrating ductal carcinoma with two patients having a metaplastic pathological subtype. No dose limiting toxicity was reported. Patients who received combination therapy are still alive except two dead due to progression of disease. The most common adverse effects, regardless of grade, were: anemia 25%, neutropenia, and leukopenia (20% each). In addition, neuropathy, and dyspnea were seen in 15% of patients (each). Grade 3/4 adverse effects were anemia, neutropenia, leukocytopenia, headache, fatigue and abdominal pain. There was one case of colitis (grade 2). Among evaluable combination treated patients (n=12), 5 patients (42%) initially showed objective response with a median duration of 7.1 months, while the disease control rate was 67%. However, 6 (55%) showed signs of progression later on leaving only 1 patient with CR, and another with SD. So far there is a definite increase in survival of TNBC with the combination therapy compared to historical rates of paclitaxel alone. However, the end point has not been reached yet. ConclusionsCombination of Durvalumab and Paclitaxel is safe with very promising efficacy in metastatic TNBC. Clinical trial identificationNCT02628132. Legal entity responsible for the studyHazem Ghebeh PhD and Taher Twegieri MD. FundingAstraZeneca (ESR-14-10649) and KFSH&RC (RAC# 2151-169). DisclosureAll authors have declared no conflicts of interest.

1063TiP - ENGOT-EN9/LEAP-001: A phase III, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer

BackgroundWhile early stage endometrial cancer (EC) is associated with a favorable prognosis, prognosis for advanced or recurrent EC is poor. Paclitaxel and carboplatin chemotherapy (CT) is often used as first-line treatment for these patients; however, there exists an imperative need for more effective and tolerable therapies. In KEYNOTE-146, combination therapy with the PD-1 inhibitor pembrolizumab (pembro) and the tyrosine kinase inhibitor lenvatinib resulted in an ORR of 39% in patients with EC (Makker et al. ASCO 2018). Based on these promising data, the ENGOT-EN9/LEAP-001 study was initiated to assess this combination therapy in women with recurrent or advanced EC. Trial designThe ENGOT-EN9/LEAP-001 study (NCT03884101) is a phase 3, randomized, open-label, active-controlled trial comparing combination therapy with pembro and lenvatinib to paclitaxel and carboplatin CT in patients with newly diagnosed stage III-IV or recurrent EC (NCT03884101). Approximately 720 patients not previously treated with systemic chemotherapy (except as part of a chemoradiation regimen), antiangiogenic agents, PD-1 or PD-L1 inhibitors, or other T-cell receptor–targeted agents will be randomized 1:1 to pembro (200mg Q3W) plus lenvatinib (20mg daily) or paclitaxel and carboplatin CT (pac 175mg/m2 plus carb AUC 6 Q3W). Patients will first be stratified by proficient vs deficient mismatch repair status (pMMR vs dMMR), and pMMR patients will be further stratified by ECOG performance status (0 vs 1), measurable disease (yes vs no), and prior chemoradiation (yes vs no). Treatment will continue until disease progression, initiation of new anticancer treatment, unacceptable adverse events, or withdrawal of consent for up to 35 cycles for pembro or 7 cycles of paclitaxel and carboplatin CT. Primary endpoints are PFS per RECIST v1.1, assessed by blinded independent central review, and OS. Secondary endpoints are ORR, health-related quality of life, safety and tolerability, and pharmacokinetics of lenvatinib. Exploratory endpoints include duration of response, disease control rate, and clinical benefit rate. Enrollment is ongoing. Clinical trial identificationNCT03884101; 21, 2019. Editorial acknowledgementNathan Rodeberg, PhD, and Diane Neer, ELS, of MedThink SciCom, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc. Legal entity responsible for the studyMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA, are responsible for the governance, coordination and running of the study. FundingFunding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA. DisclosureC. Vulsteke: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (self): Leo-Pharma; Honoraria (self): Merck MSD; Honoraria (self): AstraZeneca; Honoraria (self): Astellas. V. Makker: Advisory / Consultancy: Eisai; Advisory / Consultancy: Merck; Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: ArQule; Research grant / Funding (self): Karyopharm; Research grant / Funding (self): AstraZeneca. I.A. McNeish: Honoraria (self): Clovis Oncology; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Tesaro. L. Dutta: Full / Part-time employment: Eisai. C. Xu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. S.M. Keefe: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. J. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. S. Pignata: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Honoraria (self): Clovis Oncology; Honoraria (self): Tesaro; Honoraria (self): Inctre. All other authors have declared no conflicts of interest.

Ovarian Sertoli-Leydig Cell Tumors: Epidemiological, Clinical and Prognostic Factors.

To describe a series of cases of ovarian Sertoli-Leydig cell tumors (SLCTs). Retrospective review of 12 cases of SLCT treated at the Hospital do Câncer de Barretos, Barretos, state of São Paulo, Brazil, between October 2009 and August 2017. The median age of the patients was 31 years old (15-71 years old). A total of 9 patients (75.0%) presented symptoms: 8 (66.7%) presented with abdominal pain, 5 (41.7%) presented with abdominal enlargement, 2 (16.7%) presented with virilizing signs, 2 (16.7%) presented with abnormal uterine bleeding, 1 (8.3%) presented with dyspareunia, and 1 (8.3%) presented with weight loss. The median preoperative lactate dehydrogenase (LDH) was 504.5 U/L (138-569 U/L), alpha-fetoprotein (AFP) was 2.0 ng/ml (1.1-11.3 ng/ml), human chorionic gonadotropin (β-hCG) was 0.6 mUI/ml (0.0-2.3 mUI/ml), carcinoembryonic antigen (CEA) was 0.9 ng/ml (0.7-3.4 ng/ml), and cancer antigen 125 (CA-125) was 26.0 U/ml (19.1-147.0 U/ml). All of the tumors were unilateral and surgically treated. Lymphadenectomy was performed in 3 (25.0%) patients, but none of the three patients submitted to lymphadenectomy presented lymph node involvement. In the anatomopathological exam, 1 (8.3%) tumor was well-differentiated, 8 (66.7%) were moderately differentiated, and 3 (25.0%) were poorly differentiated. A total of 5 (55.6%) tumors were solid-cystic, 2 (22.2%) were purely cystic, 1 (11.1%) was cystic with vegetations, and 1 (11.1%) was purely solid, but for 3 patients this information was not available. The median lesion size was 14.2 cm (3.2-23.5 cm). All of the tumors were at stage IA of the 2014 classification of the International Federation of Gynecology and Obstetrics (FIGO). A total of 2 (16.7%) patients received adjuvant treatment; 1 of them underwent 3 cycles of paclitaxel and carboplatin every 21 days, and the other underwent 4 cycles of ifosfamide, cisplatin and etoposide every 21 days. None of all of the patients had recurrence, and one death related to complications after surgical staging occurred. Abdominal pain was the most frequent presentation. There was no ultrasonographic pattern. All of the SLCTs were at stage IA, and most of them were moderately differentiated. Relapses did not occur, but one death related to the surgical staging occurred.

A preliminary results of integrated chemotherapy with EGFR receptor tyrosine kinase inhibitors in patients with non-small-cell-lung cancer harboring EGFR mutation

In the open prospective non-randomized single-center study we recruited patients with advanced NSCLC harboring EGFR mutations. Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The primary endpoint was progressive free survival (PFS) time. One-year PFS in all patients group included in the study at the time of the preliminary analysis was 79.8%, median PFS was 17 months (13.5–23, CI 95%). In the group of integrated chemotherapy one-year PFS was 89.3%, median PFS was 19 months (14–23.5, CI 95%).

Paclitaxel/carboplatin with or without cetuximab for treatment of carcinoma with unknown primary (PACET-CUP): Results of a multi-center randomized phase II AIO trial.

4120 Background: Paclitaxel/carboplatin is one of the standard regimens for empiric treatment of patients (pts) with carcinoma with unknown primary (CUP) when a specific therapy is not available. The EGFR antibody cetuximab demonstrated efficacy in several cancer types. Methods: Pts with newly diagnosed non-resectable, undifferentiated or adeno-CUP were randomized to 6 cycles paclitaxel 175 mg/m² and carboplatin AUC 5 every three weeks (arm A) or the same chemotherapy plus cetuximab (400 mg/m², then 250 mg/m² weekly; arm B) at 13 German centres. CUP pts belonging to favorable prognosis groups [i.e. women with isolated peritoneal carcinomatosis or axillary lymph node metastases, men with retroperitoneal lymph nodes, pts with specific tumor entities according to histology / immunohistochemistry] were excluded from the trial. The primary endpoint was progression-free survival (PFS), secondary endpoints were response rate (RR) and overall survival (OS). Results: Between 03/2010 and 03/2017, 72 pts were randomized to arm A and 78 pts to arm B. The median age was 61 years, 84 pts were male (40 and 44 pts in arm A and B). 58 pts had a performance status (PS) of 0 (24 and 34 pts), 89 pts a PS of 1 (47 and 42 pts in arm A and B), and one patient in arm A had a PS of 2. PFS and OS did not differ between arms. The median PFS was 3.7 [95%CI: 3.0 - 4.4] and 4.6 [95%CI: 2.9 - 6.2] months in arms A and B (HR 0.98 [95%CI: 0.70-1.37]), the median OS 8.1 [95%CI: 6.5 - 9.8] and 7.4 [95%CI: 5.1 - 9.6] months in arms A and B, respectively (HR 1.10 [95%CI: 0.77 - 1.56]). There was a statistically non-significant trend towards a higher RR with cetuximab: 11 pts had a partial response in arm A (15% [95%CI: 7.9 - 26%]), and 17 pts in arm B (22% [95%CI: 13%-33%], p = 0.30). Twenty-five pts in each arm had stable disease, and 36 pts in each arm had progressive disease or were not evaluable for response. Conclusions: This study represents one of the largest trials in pts with CUP and demonstrates that randomized trials are feasible in this disorder with high medical need. The outcome of CUP pts in the unfavorable prognosis group was not improved by adding cetuximab to empiric therapy paclitaxel/carboplatin. Clinical trial information: NCT00894569.

Evaluation of Therapeutic Efficacy and Health Related Quality of Life of Anthracyclines Regimen and Taxanes with Anthracyclines Regimen in Node Positive Breast Cancer

Background: Chemotherapy with anthracyclines/taxanes is considered as an effective treatment option for breast cancer. Adjuvant chemotherapeutic options with anthracyclines or taxanes have improved disease free survival and overall survival rates in early breast cancer. The study is aimed to compare the therapeutic efficacy of anthracyclines containing regimen and sequential administration of taxanes with anthracyclines regimen for NODE positive breast cancer patients and to assess the Health-Related Quality of Life (HRQOL) of treated patients. Methods: This prospective open label study involved 14 patients who were treated with 6 cycles of 5-Fluorouracil (500mg/m2 ), Doxorubicin (50mg/m2 ), Cyclophosphamide (500mg/m2 ) [FAC] and 10 patients with 6 cycles of FAC plus 4 cycles of Paclitaxel (225mg/m2 ) [PAC]. Paired sample T test was used to assess the disease-free survival and reoccurrence rate. Time to progression was assessed by Kaplan Meir analysis and independent sample T test was used for assessing all the HRQOL parameters. Results: The disease-free survival was evaluated between the baseline and after 2 months of the chemotherapy which showed significant difference (p Key words: Anthracyclines, Adjuvant therapy, Breast cancer, Disease free survival, HRQOL, Taxanes.

Efficacy of gabapentin for the prevention of paclitaxel induced peripheral neuropathy: A randomized placebo controlled clinical trial.

Neuropathy is a dose limiting side effect of taxanes which may impact the quality of life and treatment outcomes. This randomized placebo-controlled double-blinded clinical trial was carried out to assess the efficacy of gabapentin in preventing chemotherapy induced neuropathy. Women with breast cancer were randomized into two groups of paclitaxel chemotherapy with gabapentin 300mg/three times a day orally or placebo for 2weeks started at day 1 of each paclitaxel cycle. Two groups were compared based on the relative frequency of neuropathy and change in nerve conducting velocity (NCV). Twenty women were assigned to each study arm. The majority of the neuropathy in gabapentin group was grade 1 in all of the four cycles with no event of ≥grade 3 neuropathy in this group. Compared to the placebo, the rate of 2nd and 3rd grade neuropathy was significantly lower in the gabapentin group (P=0.000). The change in NCV after four cycles of paclitaxel was significantly lower in the gabapentin group compared to the placebo group (17.7% vs 61.0% decline in NCV for sural and 21.9% vs 62.5% declines in NCV for peroneal nerve). Gabapentin given with paclitaxel is effective in the prevention of intermediate and high grade neuropathies both objectively and subjectively.

Abstract P1-13-01: Final results of the ASG1-3 study, a randomized phase III study comparing a standard dose chemotherapy with epirubicin/cyclophosphamide and paclitaxel with a dose dense regimen with epirubicin and paclitaxel

Abstract Background Dose dense chemotherapy (DDT) has shown improvements of disease-free survival (DFS) and overall survival for primary breast cancer patients with a high risk of relapse. There are much less data about the effect of DDT in patients with intermediate risk of recurrence (1-3 positive axillary lymph nodes). Aim of this prospectively randomized trial was to investigate the superiority of a DDT schedule over a standard chemotherapy (ST) in primary breast cancer patients with 1-3 positive axillary lymph nodes. Methods The ASG1-3 study is a prospectively randomized, open label phase III study of the Adjuvant Study Group of the NOGGO association. Patients were eligible for the trial, if they had a primary invasive breast cancer (pT1-3) with 1-3 positive axillary lymph nodes and no evidence of distant metastases. Patients were randomized to an adjuvant therapy with either 4 cycles epirubicin (90mg/m2 body surface area, BSA) and cyclophosphamide (600mg/m2 BSA) q3w, followed by 4 cycles of paclitaxel (175mg/m2 BSA) referred to as ST or to a therapy with 4 cycles of epicubicin (120 mg/m2 BSA) q2w and primary G-CSF support followed by 4 cycles of paclitaxel (175mg/m2 BSA) q2w and primary G-CSF support referred to as DDT. Trastuzumab was not given in this study. The study was designed to show an increase of 70% DFS (ST) to 80% DFS (DDT) 5 years after randomization. Comparisons were conducted using Kaplan Meier estimates, log rank tests and Cox regression analyses. In an exploratory way, subgroup analyses were performed for HER2, hormone receptor status and grading using Cox regression models with interaction terms. Results A total of 936 patients were eligible for survival analysis, of which 465 were randomized to ST and 471 to DDT from 2001 to 2004. Patient characteristics were mainly well balanced, with patients being 52.5/52.1 years old, 71.9/78.1% being hormone receptor positive, 24.4/24.6% being HER2 positive and 38.6/38.8% having a tumor grade of 3 in the ST arm and DDT arm respectively. 53 events occurred after ST and 46 after DDT. Adjusted hazard ratio (HR) was 0.87 (95%CI: 0.57-1.35; p=0.54). 5 year DFS rates were 85% (ST) vs. 87% (DDT). Hematological toxicities were the most common grade 3 or 4 adverse events. Grade 3/4 neutropenia occurred in 57.2 vs. 28.0%, grade 3/4 anemia in 15.3% vs. 17.1% and grade 3 /4 pain symptoms were seen in 13.2 vs. 12.4% of the patients in the ST arm vs. DDT arm respectively. Other grade 3/4 toxicities were less frequent than 10%. Subgroup analysis showed a significant interaction (p&amp;lt;0.001) between HER2 status and randomization arm with regard to DFS. In HER2 negative patients the HR was 1.53 (95%CI: 0.91-2.59), whereas in HER2 positive patients the HR was 0.22 (95%CI: 0.09-0.55). Patients with HER2 positive disease and DDT had a similar prognosis like HER2 negative patients. Conclusion In the overall population a statistically significant improvement of DFS could not be shown for the DDT arm. In patients with HER2 positive breast cancer DDT chemotherapy improved the disease-free survival to a prognosis which was similar to patients with HER2 negative disease. Citation Format: Fasching PA, Eggemann H, Krocker J, Häberle L, Volz B, Kleine-Tebbe A, Blohmer J-U, Kittel K, Hufnagel M, Janni W, Emons G, Simon E, Köhler U, Thomssen C, Kohls A, Beckmann MW, Hielscher C, Krabisch P, Zeiser T, Brodkorb T, Baier F, Nabieva N, Kellner S, Untch M, Stadie S, Budner M, Breitbach G-P, Keller M, Stickeler E, Kühn T, Tolkmitt M, Belau AK, Schmidt M, Ulm K, Kümmel S. Final results of the ASG1-3 study, a randomized phase III study comparing a standard dose chemotherapy with epirubicin/cyclophosphamide and paclitaxel with a dose dense regimen with epirubicin and paclitaxel [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-01.

Radium-223 in combination with paclitaxel in cancer patients with bone metastases: safety results from an open-label, multicenter phase Ib study

PurposeConcomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel.MethodsEligible patients had solid tumor malignancies with ≥2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m2 per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1).ResultsOf 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast (n = 7), prostate (n = 4), bladder (n = 1), non–small cell lung (n = 1), myxofibrosarcoma (n = 1), and neuroendocrine (n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population.ConclusionRadium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases.

Dorsal root ganglion explants derived from chemotherapy-treated mice have reduced neurite outgrowth in culture

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and debilitating adverse effect of cancer therapy that results from treatment with neurotoxic agents. Although chemotherapy treatment has been shown to inhibit neurite outgrowth from dorsal root ganglion (DRG) neurons in vitro, evidence for this effect in vivo is lacking. In this study, we investigated whether chemotherapy treatment in mice alters the capacity for axonal outgrowth from ex vivo cultured DRG explants. Using a neurite outgrowth assay, we demonstrated that DRG explants isolated at day 30 from mice treated with 6 cycles of paclitaxel, or 12 cycles of oxaliplatin showed a significant reduction in neurite outgrowth as compared to DRG explants from control vehicle-treated mice. DRGs that were isolated at day 90 showed recovery of the neurite outgrowth, and no significant differences were detected in comparison to vehicle controls. These results are corroborated with an in vitro model, whereby direct application of oxaliplatin and paclitaxel dose-dependently reduced neurite outgrowth of DRG explants. In conclusion, our results show that the effect of paclitaxel and oxaliplatin on the structural plasticity of DRG is retained ex vivo (for at least 30 days) and suggest the use of DRG explants derived from chemotherapy-treated mice as an efficient method to investigate the mechanisms underlying CIPN and test for possible therapeutic targets.

Adjuvant Pelvic Radiation “Sandwiched” Between Paclitaxel/Carboplatin Chemotherapy in Women With Completely Resected Uterine Serous Carcinoma: Long-term Follow-up of a Prospective Phase 2 Trial

We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation "sandwiched" between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival. Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities. One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles. The long-term follow-up in this study demonstrates that "sandwich" therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal "sandwich" therapy should be considered in all USC patients who have undergone complete surgical resection and staging.

A Rare Case of Primary Ovarian Squamous Cell Cancer Metastatic to Colon

Metastatic lesions of the colon are rare and can be challenging in management. The incidence of these metastases appears to be increasing, as a result of increasing awareness and screening for colonic cancer. Colonic metastases of ovarian origin account for 4-6% of cases. We present a unique case of pure primary ovarian in situ squamous cell carcinoma (SCC) that presented with metastasis to the colon. A 66-year-old female from the Caribbean with a history of in situ ovarian SCC with bilateral oophorectomy about a year ago, presented with complaints of diffuse abdominal pain for 1 week with associated nausea, vomiting, and constipation. Physical exam was remarkable for abdominal distension. Initial labs were unremarkable. A Computed Tomography scan of the abdomen and pelvis revealed moderate distention of the transverse and right colon. Right colon was dilated to 9.4 cm with gradually tapering to the level of the mid sigmoid colon (Fig 1). With concern for intestinal obstruction, the patient had an exploratory laparotomy. Findings on surgery included multiple adhesions which were extensively lysed. A dilated cecum requiring cecostomy and a rectosigmoid mass which was removed en-bloc.Pathology of the rectosigmoid mass revealed metastatic squamous cell carcinoma, with moderate differentiation extending through the colonic wall (Fig 2,3).Patient was started on palliative chemotherapy with 4 cycles of paclitaxel combined with carboplatin and is responding to chemotherapy.1567_A Figure 1. Colonic dilation secondary to obstruction1567_B Figure 2. Arrow showing carcinoma cells on H&E stain1567_C Figure 3. Arrow showing squamous cancer cells on immunohistochemical stain with P63SCC of the ovary may be metastatic in 2% of all the ovarian cancers. Metastatic ovarian cancer, to colon or rectum, are extremely rare. Spread of ovarian neoplasm to the colon and rectum may involve a lymphogenous, hematogenous route, direct infiltration of the bowel wall, or through the peritoneum. The interval between the initial diagnosis and the development of metastases to the colon is variable with a mean interval of 9 years. However synchronous manifestation of colonic metastasis with ovarian carcinoma has been described. Immunohistochemical staining positive for CK7, CA-125, estrogen and progesterone receptors is considered indicative of an ovarian origin of the mass. This case is a unique case of pure primary ovarian in-situ carcinoma that presents within a short duration as metastatic SCC of the colon. This case highlights the significance of recognizing that not all colonic mass are primary colorectal carcinoma.

A Phase I Evaluation of Extended Field Radiation Therapy With Concomitant Cisplatin Chemotherapy Followed by Paclitaxel and Carboplatin Chemotherapy in Women With Cervical Carcinoma Metastatic to the Para-aortic Lymph Nodes: An NRG Oncology/Gynecologic Oncology Group Study

BackgroundChemo-radiation (chemoRT) has improved the overall survival for locally advanced cervical cancer (LACC) though women whose disease involves the para-aortic nodes (PAN) experience recurrence rates and worse survival outcomes compared to those without PAN involvement. This Phase I study determined if additional cycles of systemic chemotherapy could be safely added to extended field chemoRT in this population of patients. MethodsWomen with LACC and documented positive PAN were eligible for treatment. All women were treated with extended field radiation and brachytherapy and concurrent cisplatin 40 mg/m2 weekly for six weeks. Four to six weeks after completion of chemoRT, patients were treated with four cycles of paclitaxel 135 mg/m2 and escalating doses of carboplatin (Dose Level (DL) 1 = AUC 4, DL2 = AUC 5). ResultsEleven women were entered on study and 9 were evaluable for dose limiting toxicities (DLT). Two women (1 in each of 2 DLs) did not complete chemoRT and so were not evaluable for DLT. Three women completed all 10 cycles at DL 1 with no DLTs. Six women were then treated at DL 2. For the 10 patients evaluable for response, the ORR was 60% (CR + PR). PFS and OS at 12 months were 60% and 90%, respectively. The predominant grade 3 or 4 acute toxicities were hematologic. There were no grade 5 events. ConclusionExtended field chemoRT followed by paclitaxel 135 mg/m2 and carboplatin AUC 5 is feasible in women with LACC and positive PAN.

Intermittent versus continuous first-line treatment for HER2-negative metastatic breast cancer: the Stop & Go study of the Dutch Breast Cancer Research Group (BOOG).

We determined if intermittent first-line treatment with paclitaxel plus bevacizumab was not inferior to continuous treatment in patients with HER2-negative, advanced breast cancer. Patients were randomized to 2 × 4 cycles or continuous 8 cycles of paclitaxel plus bevacizumab, followed by bevacizumab maintenance treatment until disease progression or unacceptable toxicity. The primary endpoint was overall progression-free survival (PFS). A proportional-hazards regression model was used to estimate the HR. The upper limit of the two-sided 95% CI for the HR was compared with the non-inferiority margin of 1.34. A total of 420 patients were included with well-balanced characteristics. In the intention-to-treat analysis, median overall PFS was 7.4months (95% CI 6.4-10.0) for intermittent and 9.7 months (95% CI 8.9-10.3) for continuous treatment, with a stratified HR of 1.17 (95% CI 0.88-1.57). Median OS was 17.5 months (95% CI 15.4-21.7) versus 20.9 months (95% CI 17.8-24.0) for intermittent versus continuous treatment, with a HR of 1.38 (95% CI 1.00-1.91). Safety results and actually delivered treatments revealed longer durations of treatment in the continuous arm, without significant unexpected findings. Intermittent first-line treatment cannot be recommended in patients with HER2-negative advanced breast cancer. EudraCT 2010-021519-18; BOOG 2010-02.

Esophageal metastasis from endometrial adenocarcinoma: a case report and literature review

: Esophageal metastasis from a primary lesion is considered rare, especially when deriving from endometrial adenocarcinomas. Here, we describe a case of a 58-year-old woman presenting with a 3-month history of progressive dysphagia and lower abdominal pain. Subsequently, a poorly differentiated esophageal carcinoma was confirmed by endoscopic biopsy. The pathological and immunohistochemical analyses of the esophageal lesion were similar to that of the endometrial adenocarcinoma that had been removed 2 years earlier, suggesting that the esophageal tumor derived from her previous endometrial adenocarcinoma. The patient received 6 cycles of paclitaxel plus carboplatin first-line chemotherapy and 2 cycles of epirubicin plus cisplatin second-line chemotherapy, with continued disease progression. After switching to apatinib, computed tomography (CT) scans revealed stable disease after 2 months of treatment. Our goal in this case report was to increase the awareness of clinicians and pathologists regarding the possibility of esophageal metastasis originating from endometrial adenocarcinoma, although it is a rare occurrence. Apatinib may be effective for treating metastatic endometrial carcinoma. However, further investigations are warranted to determine the optimal targeted agent for this condition.

A Case Report of Cerebral Venous Thrombosis after Taking Tamoxifen in Breast Cancer Patient

Background: Tamoxifen is commonly used in adjuvant treatment in hormonal receptor positive breast cancer patients. Cerebral venous thrombosis is one of the rare adverse events from tamoxifen. Report of the case: A 52-year-old lady was diagnosed right breast cancer (stage T3N3M0). She was undergone right modified radical mastectomy. The pathological results revealed invasive lobular carcinoma, size 6x2.3x2 cm. , grade 2, negative resected margin, ten out of fifteen lymph nodes were positive for malignancy. The immunohistochemistry was ER 90%, PR 25%, Her2 negative, and Ki67 10%. She obtained adjuvant chemotherapy, 4 cycles of Doxorubicin and cyclophosphamide followed by 4 cycles of paclitaxel every 3 weeks. She was prescribed tamoxifen during adjuvant radiation to her chest wall and regional lymph nodes. Approximately 8 months after taking tamoxifen, she complained progressive headache, dizziness, nausea and vomiting. Emergency CT brain with Contrast was done to rule out brain metastases. The scan revealed hyper dense lesion at temporal area with vasogenic edema, focal filling defect at left transverse sigmoid junction and upper portion of internal jugular vein. There was no demonstrable parenchymal metastasis. MRI and MRV of the brain showed acute dural venous sinus thrombosis of the lateral aspect of the left transverse sinus, left sigmoid sinus, left upper internal jugular vein as well as cortical venous thrombosis in the left vein of Labbe. Venous infarction in the left temporal lobe and left superior cerebellar hemisphere. Causing intraparenchymal hematoma in the left lobe. Laboratory analysis was done. Protein C/S, Lupus anticoagulant, ant thrombin, homocystein, anticardiolipin IgG/IgM, anti B2 glycoprotein I-IgG/IgM was normal. She was given enoxaparin 0.6 ml SC every 12 hours and tamoxifen was off. The scan of CT brain 6 days later showed interval decreased attenuation intraparenchymal hematoma at left posterior temporal lobe. Her headache was improved and no neurological deficit was detected. Ultrasonography of both lower extremities showed no evidence of deep vein thrombosis. She then switched to aromatase inhibitors. Discussion: Clinical risk factors for venous thromboembolism are major general or orthopedic surgery, paralysis, pelvic fracture, trauma, cancer previous venous thromboembolism, cancer, major surgery, trauma, obesity, varicose veins, cardiac disease, pregnancy and nephritic syndrome. Our patient had none of these risk factors. Although it is quite rare, cerebral venous thrombosis must be kept in mind of possible adverse effect from tamoxifen.

The predictive value of sentinel node biopsy in early breast cancer after neo-adjuvant chemotherapy: A prospective study

ObjectiveA sentinel Node (SN) has replaced axillary lymph node dissection (ALND) in patients with clinically node negative axilla (cN0). SN after Neo-adjuvant chemotherapy (NACT) is feasible but not accurate in clinically node positive (cN1-3) patients. The goal of this study is to determine the negative predictive value (NPV) of SN in cN0 breast cancer after NACT. A secondary endpoint is to determine if ALND can be avoided after NACT regardless of the pre-treatment clinical staging of the axilla, in case of a normalization of the 18F-fluoro-2-deoxy-glucose positron emission tomography scan (PET-CT scan). DesignA single institution prospective study regarding the negative predictive value of the SN in breast cancer after NACT was conducted in the Multidisciplinary Breast Clinic of the Antwerp University Hospital from 29/03/2010 until 01/12/2015 (Study number: B30020108368). Inclusion criteria for study participation were: breast cancer, age above 18 years, female, tumor stages T2-T4 N0-3 or T1N1-N3. All patients were staged by a mammography, ultrasound of the axilla, MRI of the breast, PET-CT scan and bone scintigraphy. They received NACT consisting of 12 cycles of paclitaxel or 4 cycles of docetaxel followed by dose dense doxorubicin or epirubicin/cyclofosfamide or vice versa as a standard initial treatment. After 6 weeks, a PET-CT scan was performed for early tumour response evaluation. At the day of operation, a 99mTC-labelled nanocolloid was used to identify the SN. During the surgery the SN were removed separately together with a complete ALND. ResultsA total of 150 patients were enrolled in our study of which 129 were eligible for analysis. 53 patients had a positive SN of which 32 have a positive axillary lymph nodes (ALN), positive predictive value (PPV) was 60%; 76 patients had a negative SN of which 6 had a positive ALN (NPV 92%). The sensitivity is 84% and the specificity 76% with a false omission rate (FOR) of 8%. In total 45 patients ALN were clinical negative and no suspect lymph nodes were seen on ultrasound, MRI and PET-CT scan) and 45 patients had negative a SN, with no ALN and 2 patients had a positive SN of which 1 patients had axillary involvement (NPV 100%). The FOR of cN1: 5%, cN2: 37%, cN3 33%. A total of 22 patients out of 84 patients (26%) of which 15/49 cN1 (30%), 6/23 (26%) cN2, 1/12 (8%) have after 6 weeks of chemotherapy and normalization on PET-CT scan. A total of 17 patients had a negative SN and ALN. The FOR was in this group was 0%. ConclusionA SNB should become the standard after NACT if case of a cN0. If after NACT the PET CT has normalized, no ALND should be performed if the SN is negative.