المؤلفون: Vernon K. Sondak, Andrew Poklepovic, Nikhil I. Khushalani, Jason J. Luke, Sunil Babu, Sigrun Hallmeyer, Zeynep Eroglu, Mario R. Velasco, Emily F. Higgs, Bruce Brockstein, Daniel J Olson, Thomas Krausz, Madhuri Bajaj, Timothy Carll, Riyue Bao, Jose Lutzky, Theodore Karrison, Brian W. Labadie, Thomas F. Gajewski, Yuanyuan Zha

المصدر: J Clin Oncol

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Ipilimumab, Pembrolizumab, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, RAPID COMMUNICATIONS, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Melanoma, Language, Aged, Aged, 80 and over, biology, business.industry, Anti pd 1, Immunotherapy, Middle Aged, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, Antibody, business, medicine.drug

الوصف: PURPOSE Combination of antiprogrammed cell death protein-1 (PD-1) plus anti–cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy. METHODS Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non–anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR. RESULTS Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody–based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1–negative, non-T-cell–inflamed, and intermediate tumor phenotypes. CONCLUSION To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f53f50387d5994f75ceeba750e8bc2f9Test
https://doi.org/10.1200/jco.21.00079Test

المؤلفون: Mario R. Velasco, Charles Lu, Mary W. Redman, James Gilbert Hueftle, Jieling Miao, Ignacio I. Wistuba, David R. Gandara, Nicholas J. Vogelzang, Shirish M. Gadgeel, Frank V. Fossella, John V. Heymach, Brandy Box-Noriega, Anne S. Tsao, Karen Kelly

المصدر: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 37, iss 28

مصطلحات موضوعية: 0301 basic medicine, Oncology, Male, Mesothelioma, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, SWOG investigators, Pleural Neoplasms, Oncology and Carcinogenesis, Clinical Sciences, and over, Pemetrexed, law.invention, Cediranib, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, 80 and over, Humans, Progression-free survival, Oncology & Carcinogenesis, Aged, Cisplatin, Aged, 80 and over, Chemotherapy, Malignant, business.industry, Mesothelioma, Malignant, ORIGINAL REPORTS, Middle Aged, medicine.disease, Progression-Free Survival, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Quinazolines, Female, business, medicine.drug

الوصف: PURPOSE Antiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy. PATIENTS AND METHODS SWOG S0905 (ClinicalTrials.gov identifier: NCT01064648 ) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test. RESULTS Ninety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed. CONCLUSION The addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8747aaffb359ac72c1ac8b684af4b6cTest
https://pubmed.ncbi.nlm.nih.gov/31386610Test

المؤلفون: Rena Buckstein, Rakesh Gaur, Clara D. Bloomfield, Aziz Nazha, Richard Stone, Ehab Atallah, Megan Othus, Olatoyosi Odenike, Frederick R. Appelbaum, Alan F. List, Min Fang, Mario R. Velasco, Mikkael A. Sekeres, Elina K. Cook, Michael J. Rauh, Alyssa Cull, Mark R. Litzow, Diane Roulston, Eyal C. Attar, Anna Moseley, Yanming Zhang, Harry P. Erba, Steven D. Gore

المصدر: Journal of Clinical Oncology. 35:2745-2753

مصطلحات موضوعية: Adult, Oncology, Antimetabolites, Antineoplastic, Cancer Research, medicine.medical_specialty, Azacitidine, Chronic myelomonocytic leukemia, Phases of clinical research, Hydroxamic Acids, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Adverse effect, Lenalidomide, Vorinostat, Aged, Aged, 80 and over, business.industry, Myelodysplastic syndromes, Leukemia, Myelomonocytic, Chronic, Middle Aged, medicine.disease, Thalidomide, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, business, 030215 immunology, medicine.drug

الوصف: Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m2/day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). The primary phase II end point was improved ORR. Results Of 277 patients from 90 centers, 92 received azacitidine, 93 received azacitidine plus lenalidomide, and 92 received azacitidine plus vorinostat. Median age was 70 years (range, 28 to 93 years), 85 patients (31%) were female, and 53 patients (19%) had CMML. Serious adverse events were similar across arms, although combination-arm patients were more likely to undergo nonprotocol-defined dose modifications ( P < .001).With a median follow-up of 23 months (range, 1 to 43 months), the ORR was 38% for patients receiving azacitidine, 49% for azacitidine plus lenalidomide ( P = .14 v azacitidine), and 27% for azacitidine plus vorinostat ( P = .16 v azacitidine). For patients with CMML, ORR was higher for azacitidine plus lenalidomide versus azacitidine (68% v 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. ORR was higher with mutations in DNMT3A and lower for SRSF2, whereas ORR duration improved with fewer mutations. Lenalidomide dose reduction was associated with worse overall survival (hazard ratio, 1.30; P = .05). Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy, although patients with CMML benefitted from azacitidine plus lenalidomide. The efficacy of combination regimens may have been affected by dose modifications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13ebf1f5cdfe456bf32a652b5c1f9663Test
https://doi.org/10.1200/jco.2015.66.2510Test

المؤلفون: Aram F. Hezel, Katherine A. Guthrie, Cynthia G. Leichman, Howard S. Hochster, Heinz-Josef Lenz, Matthew A. Beldner, Shannon McDonough, Mario R. Velasco, Kevin G. Billingsley, Stephen R. Smalley, Charles D. Blanke

مصطلحات موضوعية: Oncology, Adult, Male, medicine.medical_specialty, Colorectal cancer, Cetuximab, Kaplan-Meier Estimate, Adenocarcinoma, Proto-Oncogene Mas, Article, Disease-Free Survival, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Aged, Performance status, business.industry, Rectal Neoplasms, Gastroenterology, Induction chemotherapy, Chemoradiotherapy, Adjuvant, Induction Chemotherapy, Middle Aged, medicine.disease, Interim analysis, digestive system diseases, Neoadjuvant Therapy, Oxaliplatin, Regimen, 030220 oncology & carcinogenesis, Female, business, medicine.drug

الوصف: Background Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patients and Methods Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. Treatment: induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Results Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Conclusion Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f883377d89e50a9ba6df5e922e379b0dTest
https://europepmc.org/articles/PMC6598683Test/

المؤلفون: Chandra P, Belani, Suzanne E, Dahlberg, Charles M, Rudin, Martin, Fleisher, Helen X, Chen, Naoko, Takebe, Mario R, Velasco, William J, Tester, Keren, Sturtz, Christine L, Hann, James C, Shanks, Manish, Monga, Suresh S, Ramalingam, Joan H, Schiller

المصدر: Cancer. 122(15)

مصطلحات موضوعية: Adult, Aged, 80 and over, Male, Lung Neoplasms, Pyridines, Antibodies, Monoclonal, Middle Aged, Antibodies, Monoclonal, Humanized, Neoplastic Cells, Circulating, Small Cell Lung Carcinoma, Article, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Anilides, Female, Cisplatin, Biomarkers, Aged, Etoposide, Neoplasm Staging

الوصف: Preclinical targeting of the hedgehog pathway by vismodegib and of insulin-like growth factor 1 receptor by cixutumumab enhances the efficacy of chemotherapy and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in small cell lung cancer.Patients with newly diagnosed extensive-stage small cell lung cancer (SCLC-ED) were randomized to receive four 21-day cycles of cisplatin and etoposide alone (cisplatin at 75 mg/m(2) on day 1 and etoposide at 100 mg/m(2) on days 1-3; arm A) or in combination with either vismodegib (150 mg/d by mouth; arm B) or cixutumumab (6 mg/kg/wk intravenously on day 1; arm C). The primary endpoint was progression-free survival (PFS). Circulating tumor cells (CTCs) were isolated/enumerated with the Veridex CellSearch platform at the baseline.One hundred fifty-two eligible patients were treated. Patient demographics and disease characteristics were well balanced between the 3 arms except for the higher rate with a performance status of 0 in arm B (P = .03). The median PFS times in arms A, B, and C were 4.4, 4.4, and 4.6 months, respectively; the median overall survival (OS) times were 8.8, 9.8, and 10.1 months, respectively; and the response rates were 48%, 56%, and 50%, respectively. None of the comparisons of these outcomes were statistically significant. The median OS was 10.5 months for those with low CTC counts (≤100/7.5 mL) at baseline and 7.2 months for those with high CTC counts (hazard ratio, 1.74; P = .006).There was no significant improvement in PFS or OS with the addition of either vismodegib or cixutumumab to chemotherapy in patients with SCLC-ED. A low baseline CTC count was associated with a favorable prognosis. Cancer 2016;122:2371-2378. © 2016 American Cancer Society.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::fe9ca690f5b9e469921f6f236bde3563Test
https://pubmed.ncbi.nlm.nih.gov/27163943Test

المؤلفون: Charles L. Shapiro, Andrew L. Himelstein, Mario R. Velasco, Ann M. O'Mara, Drew K. Seisler, Douglas Weckstein, James L. Khatcheressian, John D. Roberts, Charles L. Loprinzi, Jared C. Foster, Rui Qin, Paul J. Novotny, Tracey O'Connor, Ronald S. Go, Stephen Grubbs

المصدر: Journal of Urology. 198:484-484

مصطلحات موضوعية: Male, 0301 basic medicine, Zoledronic Acid, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Pain Measurement, Aged, 80 and over, Bone Density Conservation Agents, Diphosphonates, Imidazoles, Bone metastasis, General Medicine, Middle Aged, Metastatic breast cancer, 030220 oncology & carcinogenesis, Spinal Fractures, Female, Multiple Myeloma, medicine.drug, Adult, medicine.medical_specialty, Urology, MEDLINE, Breast Neoplasms, Bone Neoplasms, Bone and Bones, Drug Administration Schedule, Article, 03 medical and health sciences, Breast cancer, Text mining, N-terminal telopeptide, Internal medicine, medicine, Humans, In patient, Dosing, Brief Pain Inventory, Aged, business.industry, Prostatic Neoplasms, medicine.disease, Surgery, 030104 developmental biology, Zoledronic acid, Sample Size, Interval (graph theory), Osteonecrosis of the jaw, business, Spinal Cord Compression

الوصف: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ∞]; P .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.clinicaltrials.gov Identifier: NCT00869206.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9227a7abd89ebcf50e73c62ebfe10244Test
https://doi.org/10.1016/j.juro.2017.06.009Test

المؤلفون: John V. Heymach, Philip C. Mack, Karen Kelly, Mario R. Velasco, Fred R. Hirsch, Mary W. Redman, Edward S. Kim, Roy S. Herbst, James J. Moon, Shaker R. Dakhil, David R. Gandara

المصدر: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, vol 8, iss 12
Kim, ES; Moon, J; Herbst, RS; Redman, MW; Dakhil, SR; Velasco, MR; et al.(2013). Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer SWOG S0536. Journal of Thoracic Oncology, 8(12), 1519-1528. doi: 10.1097/JTO.0000000000000009. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/5v47h38xTest

مصطلحات موضوعية: Oncology, Male, Lung Neoplasms, Cetuximab, Cardiorespiratory Medicine and Haematology, Carboplatin, chemistry.chemical_compound, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Monoclonal, Clinical endpoint, Non-Small-Cell Lung, Humanized, 0303 health sciences, Middle Aged, Prognosis, 3. Good health, Survival Rate, Bevacizumab, Tolerability, 030220 oncology & carcinogenesis, Female, medicine.drug, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Paclitaxel, Clinical Sciences, Oncology and Carcinogenesis, Adenocarcinoma, Antibodies, Monoclonal, Humanized, Article, Antibodies, 03 medical and health sciences, Internal medicine, medicine, Humans, Frontline, Oncology & Carcinogenesis, Lung cancer, Survival rate, 030304 developmental biology, Neoplasm Staging, Aged, business.industry, Non–small-cell lung cancer, Carcinoma, medicine.disease, Regimen, chemistry, Feasibility Studies, business, Non-small-cell lung cancer, Follow-Up Studies

الوصف: Introduction: Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC. Methods: Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m2), cetuximab (400 mg/m2day 1 then 250 mg/m2weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m2weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner. Results: The primary endpoint of grade 4 or higher hemorrhage of 2% (95% confidence interval: 0%-7%) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56% with an overall disease control rate of 77%. Conclusion: This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819. Copyright © 2013 by the International Association for the Study of Lung Cancer.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a22cb9fee1674df9b93161b24076efabTest
https://escholarship.org/uc/item/5v47h38xTest

المؤلفون: Craig Howe, Ju Whei Lee, Mario R. Velasco, Joan H. Schiller, Chandra P. Belani, Jill M. Kolesar, Suresh S. Ramalingam, Seena C. Aisner

المصدر: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 29(13)

مصطلحات موضوعية: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Green Fluorescent Proteins, Phases of clinical research, Cetuximab, Antineoplastic Agents, medicine.disease_cause, Antibodies, Monoclonal, Humanized, Internal medicine, Original Reports, medicine, Carcinoma, Humans, Lung cancer, EGFR inhibitors, Aged, Aged, 80 and over, Performance status, business.industry, Antibodies, Monoclonal, Adenocarcinoma, Bronchiolo-Alveolar, Middle Aged, medicine.disease, Adenocarcinoma, Female, KRAS, business, medicine.drug

الوصف: Purpose Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase have demonstrated modest anticancer activity in advanced bronchioloalveolar carcinoma (BAC). We conducted a phase II study to evaluate cetuximab for the treatment of advanced BAC. Patients and Methods Patients with advanced-stage pure BAC or adenocarcinoma with BAC features, fewer than two prior chemotherapy regimens, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were eligible. Those with prior EGFR inhibitor therapy were excluded. Cetuximab was given as a weekly intravenous infusion at 250 mg/m2 after an initial loading dose of 400 mg/m2 in week 1. The primary end point was determination of response rate. EGFR and KRAS mutations were evaluated by pyrosequencing. Results Seventy-two patients were enrolled and 68 met eligibility requirements. Characteristics of patients included median age, 71 years; sex, 57% females; PS 0 or 1, 88% of patients; and smoking status, 19% never-smokers. Central pathology review confirmed the diagnosis in 45 of 49 available specimens. Approximately 50% of patients received more than two cycles of therapy (> 8 weeks). Skin rash was the most common toxicity (grade 3, 15%). The confirmed response rate was 7%, and stable disease was observed in 35%. The median survival and progression-free survival were 13 and 3.3 months, respectively. Only one of the six patients with an EGFR mutation and one of the seven patients with a KRAS mutation had a partial response. Conclusion Cetuximab was associated with modest efficacy in patients with advanced BAC, despite a low response rate. EGFR and KRAS mutations were not predictive of response to cetuximab.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3e90d93aca6d6b6e5c59b79a75f7b57Test
https://pubmed.ncbi.nlm.nih.gov/21422434Test