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1.
Victor Yazbeck Danielle Shafer Edward B. Perkins Domenico Coppola Lubomir Sokol Kristy L. Richards Thomas Shea Jia Ruan Samir Parekh Roger Strair Christopher Flowers David Morgan Maciej Kmieciak Prithviraj Bose Amy Kimball Ashraf Z. Badros Rachid Baz Hui-Yi Lin Beata Holkova 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(9):569-575.e1
Background
The proteasome inhibitor bortezomib has demonstrated marked preclinical activity when combined with the histone deacetylase inhibitor vorinostat in leukemia, multiple myeloma, and mantle cell lymphoma (MCL) cells. The present study evaluated the efficacy and safety of the combination in patients with relapsed or refractory MCL and diffuse large B-cell lymphoma (DLBCL).Patients and Methods
The present multicenter, nonrandomized phase II trial used a Simon 2-stage design with 3 cohorts: cohort A, MCL with no previous bortezomib (including untreated MCL); cohort B, MCL with previous bortezomib; and cohort C, relapsed or refractory DLBCL with no previous bortezomib. Vorinostat (400 mg) was administered orally on days 1 to 5 and 8 to 12 before bortezomib (1.3 mg/m2), which was administered intravenously on days 1, 4, 8, and 11 of each 21-day cycle.Results
For the 65 treated patients (22 in cohort A, 4 in cohort B, and 39 in cohort C), the overall response rate was 31.8%, 0%, and 7.7%, respectively. The median progression-free survival was 7.6 months for cohort A and 1.8 months for cohort C. In cohort A, 7 patients had a partial response (PRs), 5 had stable disease (SD), 7 had progressive disease (PD), 1 was not assessed, and 2 were not evaluable. In cohort B, 2 had SD and 2 had PD. In cohort C, 3 had a PR, 8 had SD, 23 had PD, and 5 were not assessed. Baseline NF-κB activation, measured as nuclear RelA by immunohistochemistry, did not correlate with clinical response.Conclusion
The combination of bortezomib and vorinostat is safe and has modest activity in MCL and limited activity in DLBCL. 相似文献2.
Stephen D. Smith Shruti Gandhy Ajay K. Gopal Prathima Reddy Mazyar Shadman Brian G. Till Ryan C. Lynch Sandra Kanan Andrew Cowan Lauren Low Brian T. Hill 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(1):48-52
Background
Initial treatment of mantle cell lymphoma (MCL) incorporating autologous stem cell transplantation affords long-term remissions, but relapses still occur. Optimal pretransplant therapy will afford high complete response rates and not impair stem cell collection. Incorporation of bortezomib represents a natural evolution of pretransplant therapy, given its proven first-line efficacy and minimal impact on stem cell collection.Patients and Methods
At the University of Washington/Seattle Cancer Care Alliance and the Cleveland Clinic Foundation, we developed modified VR-CAP/R+ara-C (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone, alternating with rituximab and high-dose cytarabine), for transplant-eligible patients with MCL. This regimen was administered as standard-of-care, pretransplant therapy to consecutive patients with MCL from April 2015 to the present.Results
A total of 37 patients were treated with this regimen, including 18 at the University of Washington/Seattle Cancer Care Alliance and 19 at the Cleveland Clinic Foundation. Most patients had intermediate- or high-risk disease by both (mantle-cell lymphoma international prognostic index (MIPI)-B and MIPI-C category. Complete response to induction was achieved in 32 (86%) of 37 evaluable patients; 2 achieved partial response, and 3 had primary refractory disease. Stem cell collection was successful in 1 attempt in 30 of 32 patients. The median follow-up of survivors measured from start of treatment is 17.4 months. Five patients have progressed, and 4 have died (2 owing to lymphoma, 2 from toxicity).Conclusion
Modified VR-CAP/R+ara-C is feasible pretransplant therapy for patients with MCL and is associated with a high rate of complete response and eligibility for autologous stem cell transplantation. 相似文献3.
Benjamin Heyman David Rizzieri David J. Adams Carlos De Castro Louis Diehl Zhiguo Li Joseph Moore Anne Beaven 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(10):679-686
Background
For patients with aggressive lymphomas who relapse after initial therapy, a durable response is rarely achieved with standard salvage therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We conducted a phase I prospective single arm clinical trial of the novel combination of BuRP (bendamustine, rituximab, and pixantrone) in patients with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL).Patients and Methods
Eligible patients included adults with biopsy-proven R/R B-cell NHL who met the criteria for treatment. Patients received bendamustine 120 mg/m2, rituximab 375 mg/m2, and pixantrone, per cohort dose, on day 1 for up to 6 cycles. Dose escalation used a 3 + 3 design, from a starting dose level of pixantrone 55 mg/m2 to 115 mg/m at dose level 3.Results
Twenty-two patients were enrolled onto the study with a median follow-up of 7.9 months. The maximum tolerated dose was not reached, but the highest dose level of pixantrone of 115 mg/m2 was well-tolerated. The most common grade 3/4 adverse events were neutropenia (27%) and thrombocytopenia (23%). The mean change in left ventricular ejection fraction was 2.5% (standard deviation, 5.51%; 95% confidence interval, 0.0%-4.9%). The overall response rate for the entire cohort was 37.5% (95% confidence interval, 15%-65%), but at the highest pixantrone dose, the overall response rate was 63%, with a complete response rate of 25%.Conclusion
The BuRP regimen was found to be safe in patients with R/R B-cell NHL. The favorable toxicity profile plus the encouraging response rates seen suggest that continued investigation of the highest dose level is warranted. 相似文献4.
Francesca De Felice Karen Llange Filippo Rubini Nadia Bulzonetti Rossella Caiazzo Daniela Musio Vincenzo Tombolini 《Clinical colorectal cancer》2018,17(1):e77-e81
Introduction
We report the treatment compliance, toxicity rates, and long-term clinical outcomes of elderly patients who received intensified neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC).Patients and Methods
We identified a retrospective cohort of patients aged ≥ 70 years with LARC who received intensified neoadjuvant CRT, followed by surgery and adjuvant chemotherapy, from 2007 to 2014. Intensified neoadjuvant CRT consisted of radiotherapy (total dose, 50.4/54 Gy) with concomitant oxaliplatin (50 mg/m2/wk) and 5-fluorouracil (200 mg/m2 in 5 daily continuous infusion).Results
A total of 26 patients were included. All patients completed the programmed CRT. Severe acute toxicity was recorded in 19.2% of cases. Conservative surgery was performed in 16 patients, and a pathologic complete response was achieved in 19.2%. Overall, 26.9% of the patients died. The 5-year overall survival and disease-free survival rates were 70.6% and 65.5%, respectively.Conclusions
Intensified neoadjuvant CRT is an efficacious and safe treatment option for LARC in elderly patients. 相似文献5.
Susan O&#x;Brien Peter Hillmen Steven Coutre Paul M. Barr Graeme Fraser Alessandra Tedeschi Jan A. Burger Marie-Sarah Dilhuydy Georg Hess Carol Moreno Paula Cramer Emily Liu Stephen Chang Jessica Vermeulen Lori Styles Angela Howes Danelle F. James Kalpesh Patel Rudolph Valentino 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(10):648-657.e15
Background
Multiple studies have demonstrated the efficacy and safety of ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). This first-in-class inhibitor of Bruton's tyrosine kinase has become a standard treatment for patients with CLL and MCL.Patients and Methods
We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with ibrutinib versus comparators. Data were pooled from 4 completed randomized controlled studies that had included 756 ibrutinib-treated and 749 comparator-treated patients with CLL/SLL or relapsed/refractory MCL. Safety analyses included reporting of AEs using crude and exposure-adjusted incidence rates.Results
The median treatment duration was 13.3 months (maximum, 28.2 months) for ibrutinib and 5.8 months (maximum, 27.3 months) for comparators. When adjusted for exposure, diarrhea, atrial fibrillation, and hypertension were the only common grade ≥ 3 AEs more often reported with ibrutinib than with the comparators. Dose reductions (7% vs. 14%) and discontinuation (12% vs. 16%) because of AEs occurred less often with ibrutinib, and deaths due to AEs occurred at similar rates (6% vs. 7%). When adjusted for exposure, the corresponding data were all lower with ibrutinib than with the comparators (0.06 vs. 0.22, 0.11 vs. 0.22, and 0.06 vs. 0.09 patient-exposure-years, respectively). The prevalence of common grade 3/4 AEs with ibrutinib generally decreased over time, with the exception of hypertension.Conclusion
These results from an integrated analysis support a favorable benefit/risk profile of ibrutinib in patients with CLL/SLL and MCL. 相似文献6.
Yazeed Sawalha Brian T. Hill Lisa A. Rybicki Danyu Sun Robert M. Dean Deepa Jagadeesh Betty K. Hamilton Aaron T. Gerds Ronald M. Sobecks Steven Andresen Hien K. Liu Navneet S. Majhail Brad Pohlman Matt E. Kalaycio Brian J. Bolwell Mitchell R. Smith 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(1):e95-e102
Background
Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone.Patients and Methods
We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC. We herein report our experience with 28 patients treated with this regimen who proceeded to AHCT, and compare their outcomes with patients treated with either standard-dose R-CHOP (n = 38) or R-HCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate, and cytarabine; n = 21), before AHCT.Results
With a median follow-up duration of 26 months, our data show that this modification of the Nordic regimen is a highly effective pre-AHCT first-line therapy for MCL (3-year progression-free and overall survival rates of 69% and 75%, respectively).Conclusion
By using a less intense induction, this regimen can serve as a platform for combined use of novel agents, with less risk of additive toxicity. 相似文献7.
Damian A. Laber Min-Bin Chen Michael Jaglal Ankita Patel Nathan Visweshwar 《Clinical genitourinary cancer》2018,16(6):473-481
Background
There are no effective chemotherapies for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has failed to respond to taxanes or patients who do not wish to receive intravenous drugs. We hypothesized that low doses of multiple medications with prolonged exposure would result in a high response rate and low toxicity.Patients and Methods
Patients with mCRPC were eligible for this phase 2 trial. The primary endpoint was a prostate-specific antigen decrease of more than 50%. CEE consisted of cyclophosphamide (50 mg/m2), etoposide (50 mg/m2), and estramustine 280 mg provided orally once a day for 14-day cycles every 28 days.Results
Fifty-two patients were enrolled and included in all evaluations. The prostate-specific antigen response rate was 46% in all patients, 53% in chemotherapy-naive subjects, and 31% after docetaxel chemotherapy. Thirty subjects had measurable lesions, 1 (3%) had complete response, 2 (7%) partial response, and 22 (73%) stable disease, for a clinical benefit of 83%. Sixty percent experienced an improvement in their performance status, and 65% reported improvement in their pain. The median overall survival was 18.6 months in all patients, 20.4 months in chemotherapy-naive patients and 11.3 months in patients whose disease progressed while receiving docetaxel therapy. Grade 3/4 treatment-related toxicities included 20% neutropenia, 10% thrombocytopenia, 10% deep-vein thrombosis, 8% anemia, 8% fatigue, 4% death, and 2% anorexia and stomatitis.Conclusion
CEE was an all-oral, easy-to-administer, and effective triple-drug therapy for patients with mCRPC. 相似文献8.
S. Gollins S. Massalha A. Mullard R.M. Williams A. Lloyd J. Morris A. Garcia-Alonso 《Clinical oncology (Royal College of Radiologists (Great Britain))》2018,30(7):409-417
Aims
This open-label prospective phase I/II dose-escalation study determined the maximum tolerated dose (MTD) and then evaluated response, safety and feasibility of a novel combination of docetaxel, cisplatinum and capecitabine (DCC) in chemotherapy-naive patients with advanced oesophago-gastric carcinoma.Materials and methods
Patients with adenocarcinoma or squamous cell carcinoma of the oesophagus or stomach, of good performance status, deemed too advanced for curative treatment, were given systematically increasing doses of 3 weekly DCC to ascertain the MTD. Phase II administered up to six cycles of DCC at the MTD, assessing response and toxicity.Results
Between November 2007 and November 2012, 15 patients were recruited into phase I and 41 into phase II. The MDT was a 21 day cycle of docetaxel 60 mg/m2 IV day 1, cisplatinum 60 mg/m2 IV day 1 and oral capecitabine 1000 mg/m2 daily in two divided doses for days 1–21. The most common phase II grade 3–4 toxicities were neutropenia 88% (10% febrile neutropenia), fatigue 15%, sensory neuropathy 10% and non-neutropenic infection 10%. The overall response rate was 51%, median progression-free survival was 7.4 months (confidence interval 6.7–9.4) and median overall survival was 10.9 months (confidence interval 7.7–13.7).Conclusion
DCC was tolerable and feasible with promising efficacy, and may be suitable for future investigation in both first-line metastatic and neoadjuvant settings. 相似文献9.
Yasuyuki Kojima Hisanori Kawamoto Toru Nishikawa Ryosuke Hayami Arata Shimo Ei Haku Kyoko Akiyama Koichiro Tsugawa 《Clinical breast cancer》2018,18(5):374-379
Background
Although several studies have shown efficacy of nanoparticle albumin-bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage and schedules were varied or used in combination and the data are still limited for weekly regimens. We evaluated the feasibility of weekly nab-paclitaxel followed by FEC (5-FU [fluorouracil], epirubicin, and cyclophosphamide) treatment feasibility as neoadjuvant chemotherapy for breast cancer.Patients and Methods
Thirty-three patients with no previous chemotherapy were enrolled to receive nab-paclitaxel 150 mg/m2 the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant treatment. The trial was powered for analyses of feasibility.Results
Twenty-five patients completed the treatment as per protocol, and the completion rate was 75.8% (95% confidence interval, 59.0-87.2; P = .44). The regimen completion group was younger than those with regimen incompletion (average 45.1 vs. 56.6 years). The pathological complete response (ypT0-is/N0) rate was 30.3% in 33 patients, which was higher in triple-negative patients (58.3%). Grade 3/4 neutropenia was seen in 48.5%, although there was no febrile neutropenia. Grade 3 peripheral neuropathy was seen in 33.3%.Conclusion
Our study showed that weekly nab-paclitaxel 150 mg/m2 3q4w followed by FEC as neoadjuvant regimen might be sufficient in efficacy, although with a relatively high severe adverse event occurrence rate. 相似文献10.
Karin Westberg Gabriella Palmer Fredrik Hjern Hemming Johansson Torbjörn Holm Anna Martling 《European journal of surgical oncology》2018,44(1):100-107
Background
The rate of local recurrence of rectal cancer (LRRC) has decreased but the condition remains a therapeutic challenge. This study aimed to examine treatment and prognosis in patients with LRRC in Sweden. Special focus was directed towards potential differences between geographical regions and time periods.Method
All patients with LRRC as first event, following primary surgery for rectal cancer performed during the period 1995–2002, were included in this national population-based cohort-study. Data were collected from the Swedish Colorectal Cancer Registry and from medical records. The cohort was divided into three time periods, based on the date of diagnosis of the LRRC.Results
In total, 426 patients fulfilled the inclusion criteria. Treatment with curative intent was performed in 149 patients (35%), including 121 patients who had a surgical resection of the LRRC. R0-resection was achieved in 64 patients (53%). Patients with a non-centrally located tumour were more likely to have positive resection margins (R1/R2) (OR 5.02, 95% CI:2.25–11.21). Five-year survival for patients resected with curative intent was 43% after R0-resection and 14% after R1-resection. There were no significant differences in treatment intention or R0-resection rate between time periods or regions. The risk of any failure was significantly higher in R1-resected patients compared with R0-resected patients (HR 2.04, 95% CI:1.22–3.40).Conclusion
A complete resection of the LRRC is essential for potentially curative treatment. Time period and region had no influence on either margin status or prognosis. 相似文献11.
Rustain Morgan Mark Perry Jennifer Kwak Alexandria Jensen Manali Kamdar 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):731-736
Introduction
Mantle cell lymphoma (MCL) is a rare subtype of non–Hodgkin lymphoma and requires both bone marrow biopsy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to correctly stage the disease at diagnosis. However, accurate identification of bone marrow involvement by lymphoma on FDG PET/CT scans has not been previously demonstrated. We hypothesized that a voxel-based analysis of the iliac bones on the FDG PET/CT scan might provide insight into bone marrow involvement.Patients and Methods
A retrospective cohort study of patients with a diagnosis of MCL who had undergone both single iliac bone marrow biopsy and FDG-PET/CT scan from 1 study site were included in the development phase (n = 10). An additional 12 patients from a second institution were included in the validation phase. Using a semiautomated workflow, a voxel-based data set of FDG uptake within the bilateral iliac bones was captured for each patient. In the development phase, empirical receiver operating characteristic curves for each data set were fit. We then identified the standardized uptake value (SUV) threshold cutpoints at which the sensitivity and specificity were optimized to 100%. In the validation phase, we evaluated the performance of these candidate SUV threshold cutpoints in 15 additional patients from a second institution.Results
We found that 1 cutpoint, > 38% of voxels with activity < 0.95, outperformed all the other candidate cutpoints, correctly classifying all patients except for 1 (overall sensitivity, 100%; specificity, 87.5%).Conclusion
The ability to correctly identify bone marrow involvement using FDG PET/CT-based voxel analysis provides promise as a novel noninvasive method of accurate staging. 相似文献12.
Julie E. Chang Lakeesha L. Carmichael KyungMann Kim Christopher Peterson David T. Yang Anne M. Traynor Jae E. Werndli Michael S. Huie Thomas A. McFarland Michael Volk Jules Blank Natalie S. Callander Walter L. Longo Brad S. Kahl 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(1):e61-e67
Introduction
VcR-CVAD was developed as an intermediate-intensity induction regimen with maintenance rituximab (MR) to improve remission durations after first-line therapy for mantle cell lymphoma (MCL) in older and younger patients with MCL.Patients and Methods
Patients with previously untreated MCL received VcR-CVAD induction chemotherapy for 6 cycles (21-day cycles). Patients achieving at least a partial response received rituximab consolidation (375 mg/m2 × 4 weekly doses) and MR (375 mg/m2 every 12 weeks × 20 doses). The primary endpoints were overall and complete response (CR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). Thirty patients were enrolled, with a median age of 61 years. There was an even distribution of patients < 60 years and ≥ 60 years. Mantle cell lymphoma international prognostic index medium- or high-risk disease was present in 60%. The overall response rate observed was 90% (77% CR/unconfirmed CR). After a median follow-up of 7.8 years, the 6-year PFS and OS were 53% and 70%, respectively. There was no difference in 6-year PFS or OS between the younger (age < 60 years) and older (age ≥ 60 years) subgroups. In a univariate analysis, lactate dehydrogenase, when analyzed for interaction with age, had a significant effect on PFS outcomes at 6 years. There were no pretreatment variables determined to have a significant effect on OS outcomes at 6 years.Conclusions
Long-term outcomes with VcR-CVAD are comparable with more intensive inductions and consolidation approaches. MCL is biologically heterogeneous, and durable remission can be achieved with intermediate intensity therapy. MR appears to contribute to these excellent outcomes. 相似文献13.
Hayley S. McKenzie Graham Mead Robert Huddart Jeff D. White Gordon J.S. Rustin Ivo M. Hennig Kelly Cozens Nadia Cross Megan Bowers Matthew J. Wheater 《Clinical genitourinary cancer》2018,16(6):458-465.e2
Background
Metastatic germ cell tumors remain potentially curable when treated with salvage chemotherapy at first relapse. In the present phase I/II study, we sought to improve on the response rate and duration of the TIP (paclitaxel, ifosfamide, cisplatin) regimen by adding gemcitabine (Gem-TIP).Materials and Methods
Twenty patients were recruited after failure of first-line cisplatin-containing chemotherapy. The primary objectives were to determine the maximum tolerated dose of gemcitabine when combined with TIP and to establish the dose intensity of the TIP drugs in this combination. The secondary objectives were the response rates, failure-free survival, and overall survival.Results
The maximum tolerated dose of gemcitabine was 1200 mg/m2. The mean relative dose intensity was 95% (95% confidence interval [CI], 90.2%-99.2%) for gemcitabine, 96% (95% CI, 92.9%-98.7%) for paclitaxel, 92% (95% CI, 84.5%-98.8%) for ifosfamide, and 94% (95% CI, 89.3%-99.0%) for cisplatin. The overall complete response rate was 50%; another 30% of the patients achieved a partial response. The 1-year failure-free survival and overall survival rates were 68% (95% CI, 43%-84%) and 89.5% (95% CI, 64%-97%), respectively.Conclusion
Gemcitabine can be added to TIP chemotherapy at the full dose, with manageable toxicity and no detrimental effect on the dose intensity of the TIP drugs. The response rate and duration were improved compared with those reported from the Medical Research Council TIP trial; further evaluation is warranted. 相似文献14.
Ernesto Ayala Julio C. Chavez Alexandra Gomez Elsa Sleiman Ambuj Kumar Mohamed A. Kharfan-Dabaja 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(8):548-551
Background
HIV-associated lymphomas (HAL) remain an important cause of morbidity and mortality in HIV patients, especially in the setting of treatment-refractory disease. Hematopoietic cell transplantation (HCT) is considered a curative option for patients with refractory HAL.Patients and Methods
We report the efficacy of autologous HCT in 20 patients with HAL [non-Hodgkin lymphoma = 14 (70%), Hodgkin lymphoma = 6 (30%)]. At the time of transplantation, the median peripheral blood CD4+ count was 226 cells/μL. HIV virus load was undetectable in 14 (70%) of 20 patients.Results
The median follow-up of surviving patients was 47 months (range, 20-119 months). The median time to neutrophil engraftment was 11 days. The median progression-free survival and median overall survival have not been reached. At 4 years after transplantation, progression-free survival and overall survival were 65% and 70%, respectively. Six patients died from disease relapse or progression (n = 5) and infection (n = 1). Nonrelapse mortality was 0 and 5% at 100 days and 4 years after transplantation, respectively.Conclusion
Autologous HCT is an effective therapy for refractory/relapsed HAL with manageable toxicity, similar to non-HIV patients. 相似文献15.
Jean Maroun Horia Marginean Derek Jonker Christine Cripps Rakesh Goel Timothy Asmis Rachel Goodwin Gabriela Chiritescu 《Clinical colorectal cancer》2018,17(2):e257-e268
Background
The objective of the present phase I study was to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan, capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with previously untreated, unresectable advanced or metastatic colorectal cancer (CRC).Patients and Methods
Patients received oxaliplatin followed by irinotecan as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID) on days 2 to 15 of a 3-week cycle. The dose ranges were explored as follows: oxaliplatin, 75 to 120 mg/m2; irinotecan, 160 to 230 mg/m2; capecitabine, 750 to 1000 mg/m2 BID. Dose escalation was performed individually for each drug at each dose level according to the type and severity of toxicity encountered in the previous cohort.Results
A total of 39 patients were enrolled at 7 dose levels and the MTD. The recommended doses for phase II evaluation were oxaliplatin 100 mg/m2, irinotecan 160 mg/m2, and capecitabine 950 mg/m2 BID. Diarrhea and febrile neutropenia were DLTs. Of the 39 enrolled patients, 26 (67%) had confirmed objective responses. The median progression-free survival was 11 months, and the median overall survival was 25 months. The survival rate at 5 years was 23%.Conclusion
The IXO regimen has a manageable toxicity profile with promising antitumor activity as first-line treatment of advanced and metastatic CRC. 相似文献16.
Yi-Long Wu Lecia V. Sequist Eng-Huat Tan Sarayut L. Geater Sergey Orlov Li Zhang Ki Hyeong Lee Chun-Ming Tsai Terufumi Kato Carlos H. Barrios Martin Schuler Vera Hirsh Nobuyuki Yamamoto Kenneth O’Byrne Michael Boyer Tony Mok Barbara Peil Angela Märten Keunchil Park 《Clinical lung cancer》2018,19(4):e465-e479
Background
Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC).Patients and Methods
Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.Results
Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations.Conclusions
Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age. 相似文献17.
Won Kyung Cho Doo Ho Choi Won Park Hyejung Cha Seok Jin Nam Seok Won Kim Jeong Eon Lee Jonghan Yu Young-Hyuck Im Jin Seok Ahn Yeon Hee Park Ji-Yeon Kim Soohyun Ahn 《Clinical breast cancer》2018,18(5):e1141-e1147
Purpose
To investigate the effect of body mass index (BMI) on survival in patients with breast cancer according to tumor subtype, metabolic syndrome, and systemic treatment.Patients and Methods
We identified 5668 patients who underwent curative surgery for breast cancer between 1996 and 2013 from the clinical data of a single institution. Disease-free survival (DFS) and overall survival (OS) were calculated and compared between the patients with BMI ≥ 25 kg/m2 and < 25 kg/m2 in all patients and in specific subgroups, including tumor subtype, metabolic syndrome, and systemic treatment.Results
In all patients, BMI ≥ 25 kg/m2 was an unfavorable factor for OS (P = .030) but not for DFS. In the HR+/HER2? subgroup, DFS and OS were longer in patients with BMI < 25 kg/m2 than ≥ 25 kg/m2 (P = .012 and .005, respectively). In patients with more than one metabolic syndrome, BMI was an unfavorable factor for OS (hazard ratio, 2.669; P < .001)Conclusion
BMI ≥ 25 kg/m2 was an unfavorable survival factor, particularly in patients with HR+/HER2? breast cancer. 相似文献18.
Angelina Cistaro Laura Cassalia Cinzia Ferrara Natale Quartuccio Laura Evangelista Maurizio Bianchi Franca Fagioli Gianni Bisi Sergio Baldari Alessandro Zanella Marta Pillon Pietro Zucchetta Marta Burei Alessandra Sala Luca Guerra Priscilla Guglielmo Roberta Burnelli Stefano Panareo Giuseppe Rubini 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(6):e267-e273
Introduction
The present study investigated the utility of fluorine-18 (18F) fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL).Patients and Methods
A total of 224 pediatric patients with HL underwent 18F-FDG PET/CT at staging. BMB or follow-up imaging was used as the standard of reference for the evaluation of BMI.Results
18F-FDG PET/CT was negative for BMI in 193 cases. Of the 193 patients, the findings for 16 were originally reported as doubtful and later interpreted as negative for BMI, with negative findings on follow-up imaging and BMB. At BMB, 1 of the 16 patients (6.25%) had BMI. Of the 193 patients, 192 (99.48%) had negative BMB findings. Thus, the 18F-FDG PET/CT findings were truly negative for 192 patients and falsely negative for 1 patient for BMI.Conclusion
18F-FDG PET/CT showed high diagnostic performance in the evaluation of BMI in pediatric HL. Thus, BMB should be ideally reserved for patients presenting with doubtful 18F-FDG PET/CT findings for BMI. 相似文献19.
Leslie Padrnos Brenda Ernst Amylou C. Dueck Heidi E. Kosiorek Brenda F. Ginos Angela Toro Patrick B. Johnston Thomas M. Habermann Jose F. Leis Joseph R. Mikhael Grzegorz S. Nowakowski Joseph Colgan Luis Porrata Stephen M. Ansell Thomas E. Witzig Craig Reeder 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(10):664-672.e2
Background
Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non-Hodgkin lymphomas.Patients and Methods
The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination. Stem cell transplantation had failed in 27 of the patients (49%), 63% had stage IV disease, and ≥ 3 previous therapies had failed in 78%.Results
Of the 58 patients, enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade ≥ 3 toxicities were hematologic and included neutropenia (56%), leukopenia (38%), and thrombocytopenia (33%). Seven patients discontinued the study because of adverse events. One patient died of disease progression. The overall response rate was 27% (15 of 55), with 38% (21 of 55) having stable disease.Conclusion
The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has shown the combination to be tolerable, with neutropenia as the main dose-limiting toxicity. Encouraging responses were seen in this heavily pretreated group, and the patients with a response had meaningful duration of response. 相似文献20.
Abhishek Maiti Maryam Nemati-Shafaee Pavlos Msaouel Lance C. Pagliaro Eric Jonasch Nizar M. Tannir Amishi Y. Shah 《Clinical genitourinary cancer》2018,16(1):e47-e57