Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 – completely incorrect to 6 – completely correct) and completeness (3-point Likert scale; range 1 – incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; p<0.01). Conclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.
Purpose: To evaluate AZD4635, an adenosine A2A receptor antagonist, as monotherapy or in combination with durvalumab in patients with advanced solid tumors. Experimental design: In phase 1a (dose escalation), patients had relapsed/refractory solid tumors; in phase 1b (dose expansion), patients had checkpoint-inhibitor-naïve metastatic castration-resistant prostate cancer (mCRPC) or colorectal carcinoma (CRC); non-small cell lung cancer (NSCLC) with prior anti-PD-1/PD-L1 exposure; or other solid tumors (checkpoint-naïve or prior anti-PD-1/PD-L1 exposure). Patients received AZD4635 monotherapy (75–200 mg QD or 125 mg BID) or in combination with durvalumab (AZD4635 75 or 100 mg QD). The primary objective was safety; secondary objectives included antitumor activity and pharmacokinetics; exploratory objectives included evaluation of an adenosine gene signature in mCRPC patients. Results: As of September 8, 2020, 250 patients were treated (AZD4635, n=161; AZD4635+durvalumab, n=89). In phase 1a, DLTs were observed with monotherapy (125 mg BID; n=2) and with combination treatment (75 mg; n=1) in patients receiving nanosuspension. The most common treatment-related AEs included nausea, fatigue, vomiting, decreased appetite, dizziness, and diarrhea. The RP2D of the AZD4635 capsule formulation was 75 mg QD, as monotherapy or in combination with durvalumab. The pharmacokinetic profile was dose-proportional, and exposure was adequate to cover target with 100 mg nanosuspension or 75 mg capsule QD. In patients with mCRPC receiving monotherapy or combination treatment, tumor responses (2/39 and 6/37, respectively) and PSA responses (3/60 and 10/45, respectively) were observed. High versus low blood-based adenosine signature was associated with median PFS of 21 weeks versus 8.7 weeks. Conclusions: AZD4635 monotherapy or combination therapy was well-tolerated. Objective responses support additional phase 2 combination studies in mCRPC patients.
Purpose Dasatinib has been shown preclinically to overcome resistance to gemcitabine. We evaluated the safety and biological activity of the combination of dasatinib and gemcitabine in patients with advanced solid tumors. Experimental Design In a phase 1 study (3+3 design), patients received daily dasatinib with weekly gemcitabine on days 1, 8 and 15 of a 28-day cycle (except cycle 1 which was eight weeks). Dose escalation began with dasatinib 70mg orally (PO) daily and gemcitabine 800mg/m2 intravenously (IV) weekly. Results Forty-seven patients (15 men; median age = 55 years; median number of prior systemic treatments = 4) were enrolled. Dose-limiting toxicities were grade 3 fatigue and dehydration, with the maximum tolerated dose being dasatinib 100mg PO qd and gemcitabine 600mg/m2 IV weekly. The most common grade 3–4 toxicities were anemia (21.5%), thrombocytopenia (26.2%), leukopenia (26.2%), and pleural effusion (10.7%). Six of 47 patients attained stable disease (SD) ≥ 6 months or partial response including 2 of 8 patients with pancreatic cancer (SD ≥ 6 months; both gemcitabine-refractory), 2 of 3 patients with thymoma (SD for 9.8 and 15 months), 1 of 1 patient with anal squamous cancer (SD 15 months) and 1 of 5 patients with inflammatory breast cancer. No significant changes in circulating tumor cells or interleukin-8 levels were observed. Conclusions The combination was well tolerated at doses of dasatinib 100mg PO daily and gemcitabine 600mg/m2 IV weekly. SD ≥ 6 months/ PR was observed in gemcitabine-refractory pancreatic cancer, thymoma, anal cancer and inflammatory breast cancer.
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