Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 ...blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates.
Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy.
Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells > or = 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.
Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 ...blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates.
Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy.
Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.
Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
Background
To determine if pretreatment quality of life is associated with performance status in patients with pancreatic and periampullary tumors.
Methods
Eighty consecutive patients evaluated for ...surgical treatment of pancreatic or periampullary tumors completed the social functioning SF-36, a generic quality of life instrument. This instrument measures 8 domains of quality of life: physical functioning (PF), role-physical (RP), role-emotional, bodily pain, vitality, mental health, social functioning, and general health (GH). The best possible score is 100 and the worst possible score is 0. Each patient was then assigned a Karnofsky performance score (KPS), with the best possible score of 100 (normal, no complaints, no evidence of disease) and worst score of 0 (dead). Data recorded included age, gender, pathology, stage, resection, use of chemotherapy, and radiation therapy. Statistical analysis was done using single and multiple linear regression analysis, correlation coefficients (
r
) and coefficient of determination (
r
2
).
Results
KPS was significantly associated with all domains of the SF-36 by single linear regression. By multiple linear regression, KPS was significantly associated with the PF domain (
p
< 0.001,
r
= 0.74), and nearly significantly associated with the RP (
p
= 0.07,
r
= 0.62) and GH (
p
= 0.06,
r
= 0.64) domains. This appears to be independent of tumor pathology and stage.
Conclusion
The results imply that pretreatment quality of life and performance status are related concepts in patients with pancreatic and periampullary tumors. This is primarily true for the physical component of the SF-36. However, despite statistical significance, coefficients of determination (
r
2
values) suggest that there are additional factors determining both quality of life and performance status in patients with pancreatic and periampullary tumors.
Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, ...pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective.
Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy.
A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti-PD-1 therapy.
These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.
A case of a fatal hypersensitivity reaction to gemtuzumab ozogamicin in a patient who received a platelet transfusion on the same day is presented.
A 75-year-old man went to a hematology clinic in ...April 2005 because of anemia and thrombocytopenia. He was diagnosed with acute myelogenous leukemia (AML). In May 2005, the patient was started on induction chemotherapy with cytarabine and idarubicin. During the induction phase, the patient received platelet transfusions on multiple occasions without any evidence of transfusion reactions. He went into partial remission and received two cycles of cytarabine and idarubicin followed by one cycle of high-dose cytarabine. In March 2006, the patient relapsed, and he received dose number one of the first cycle of gemtuzumab ozogamicin at a dose of 9 mg/m2 on March 28, 2006. He tolerated the infusion. He had received multiple platelet transfusions during the week before gemtuzumab infusion without reaction but received no transfusions on the same day as the gemtuzumab infusion. On April 4, 2006, the patient received an infusion of gemtuzumab at 11 a.m., and he received 6 units of leukocyte-depleted, irradiated platelets at 6:40 p.m. At 1 a.m. the next morning, the patient developed fever and shortness of breath and went into severe distress. Despite treatment, the patient died shortly after.
A patient with AML developed severe respiratory distress and died after receiving gemtuzumab and 6 units of platelets on the same day. The fact that he had previously received gemtuzumab and platelets safely on separate days suggests that the gemtuzumab-platelet combination contributed to a fatal hypersensitivity reaction.
The importance of tumor angiogenesis in tumor biology is now widely accepted. Hepatocellular carcinoma (HCC) is a highly vascular tumor, and angiogenesis is believed to play a considerable role in ...its development and progression. The authors reviewed the role of circulating vascular endothelial growth factor (VEGF) in screening for HCC and in risk stratification and treatment monitoring. They searched the world medical literature by accessing MEDLINE and PubMed for articles on: 1) the utility of circulating VEGF for HCC screening in patients with cirrhosis; 2) the role of circulating VEGF as a predictor of the invasive potential of HCC; and 3) monitoring anti-HCC treatment effects by serial measurements of circulating VEGF. They found evidence to support a potential role for VEGF in screening and surveillance of HCC. They also found support for developing the use of VEGF in the monitoring of treatment outcomes. Several studies suggested that the circulating VEGF level may be an independent prognostic marker in HCC. Further studies are needed to determine the utility of circulating VEGF in screening of patients with cirrhosis and to determine its potential role as a prognostic and predictive biomarker in patients with HCC. Cancer 2009. (c) 2009 American Cancer Society.
Highlights • A Question Prompt List (QPL) to increase patient active participation in racially-discordant oncology interactions was tested. • The QPL was viewed positively by patients and did not ...affect interaction time. • The QPL booklet increased active participation but had no effect on other outcomes. • The QPL-plus-coach did not affect active participation, and decreased patient perceptions of oncologist communication. • QPLs can increase patient active participation in racially-discordant oncology interactions.
Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are ...long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease.
To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer.
Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT).
From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval CI, 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection.
Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.
Introduction: Capecitabine is an oral chemotherapy frequently used in the treatment of metastatic breast and colorectal cancers. Drug-induced cutaneous hyperpigmentation is a rare adverse effect of ...capecitabine, which is almost exclusively reported with development of hand-foot syndrome (HFS). Here, we report a case of capecitabine-induced hyperpigmentation affecting the hands, feet, face, and tongue in the complete absence of HFS.Case report: An 82-year old man presented with progressive hyperpigmentation of his hands, feet, face, and tongue shortly after initiating capecitabine for treatment of colon adenocarcinoma. There was no associated erythema, edema, blistering, desquamation, tingling, or tenderness. After completion of capecitabine therapy, he endorsed 95% resolution of all hyperpigmentation.Discussion: Previous reports of capecitabine-induced hyperpigmentation have argued that it may be a sign of impending toxicity and should be a part of the HFS grading scale. Others argue that the two are separate entities, yet the mechanism is still unknown. This case supports that capecitabine can cause hyperpigmentation independent of HFS, and thus, should be evaluated as a separate entity of HFS if other symptoms are lacking.
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