A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D51/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted. Mannitol was given before (25% solution, 50 ml bolus) and after (20% solution, 500 ml over 3 hours) CDDP. At level III hydration with the same intravenous (IV) fluids was begun the day before therapy and continued without interruption at 200 to 250 ml/hour for a minimum of 24 hours after the completion of the 5 days of chemotherapy. Each daily dose of CDDP was preceded by injection of mannitol (25% solution, 50 ml bolus) and accompanied by a 6‐hour infusion of 1000 ml 20% mannitol. Three patients received five CDDP courses at level I; 4 patients, seven courses at level II; and 5 patients, seven courses at level III. Ototoxicity was dose‐limiting in three patients at level II. Transient elevation of serum creatinine was seen following two courses at level I and two courses at level II. The renal impairment was asymptomatic in all cases; dialysis was not needed. At level II, leukocyte nadir counts between 1.0 and 2.0 × 103/mm3 were seen following two courses and between 2.0 and 3.0 × 103/mm3 following three courses. Platelet nadir counts below 50 × 103/mm3 were recorded after four courses and between 50 and 100 × 103/mm3 after one course. Nausea and vomiting occurred frequently, but were tolerable. At level III, myelosuppression was dose‐limiting. Nadir leukocyte counts between 1.0 and 2.0 × 103/mm3 followed four courses and between 2.0 and 3.0 followed one course. Nadir platelet counts below 50 × 103/mm3 were seen after three courses; two patients required prophylactic platelet transfusions. Nadirs between 50 and 100 × 103 platelets/mm3 followed three further courses. Ototoxicity and nephrotoxicity did not occur at level III. Responses were seen in all three dose levels in patients with prostate carcinoma, non‐small cell lung cancer, adenocarcinoma of the esophagus, and malignant fibrous histiocytoma. It was concluded that CDDP at a dose of 200 mg/m2, divided in five daily fractions, is tolerable and can be introduced into Phase II trials.
Eighteen patients with advanced malignancies refractory to other forms of treatment were given dactinomycin (Act D) as continuous intravenous infusions. Their median age was 51 years (range, 36-67); their median performance status was 50 (range, 40-90) on the Karnofsky scale. Act D was administered continuously for 5 days, utilizing a central venous line and a perfusion pump. The starting dose was 0.1 mg/m2/24 hours X 5 days (total dose, 0.5 mg/m2) and was escalated according to a modified Fibonacci scale to 0.2, 0.33, and 0.5 mg/m2/24 hours X 5 days, respectively. Three, three, four, and eight patients were entered, respectively, in each dose level. Toxicities observed were: leukopenia in four patients (nadir leukocyte count less than 1000 cells/nm3 in one patient and 2000-3000 cells/mm3 in 3 patients); thrombocytopenia, with nadir platelet counts between 50,000 and 100,000 platelets/mm3 in 2 patients; stomatitis in four patients; and nausea in three patients. Vomiting was not observed during the infusions. Two patients may have had a radiation recall phenomenon. Blood count depression, nausea, and mucositis were transient, resolving after a few days. One patient at level IV died of sepsis, which was diagnosed on the fourth day of the infusion, before leukopenia intervened. No objective responses were seen. It was concluded that a higher dose of Act D can be given by continuous infusion than by a bolus injection; the authors recommended 0.5 mg/m2/day X 5 days (total dose, 2.5 mg/m2) for further studies.
the experience in clinical trials. Method: We purposefully employed a soft-launch of our lung cancer screening program with low-dose CT (LDCT) so we could rapidly evaluate our experience through audit and feedback. The program began in January 2015 and included several key implementation components: 1) guideline review supporting lung cancer screening; 2) continuing medical education to physicians regarding implementation; 3) Epic-registry build to account for eligible members, orders for LDCT, completion of LDCT, and radiologic results; 4) Nurse care coordinator to follow-up with screen positive members to return for imaging; 5) Development of a shared decision making tool for patient/provider discussions. LDCT is read by radiologists using American College of Radiology Lung-RADS TM grading system. We describe the uptake of LDCT in an age-and smoking-eligible population and alignment of Lung-RADS TM with expected population estimates overall among exams conducted from 2015-2018. Negative screen is defined as Lung-RADS TM 1 or 2. Positive screen includes Lung-RADS TM 3 and 4. Result: With an estimated 15,000 adults eligible for lung cancer screening, about 1,800 annual visits have a documented shared decision-making. While the majority of patients (89%) opt-in to screening, about 26% of those patients cancel or do not show up for their LDCT exam. As of March 2018, KPWA completed 3,092 LDCT exams: 2,104 initial screens and 988 subsequent screens. Among all initial LDCT performed, 84.6% screened negative; the proportion increased slightly to 88.6% on subsequent LDCT exams. On initial LDCT, the proportion of positive exams were as follows: Lung-RADS TM 3 (7.8%); Lung-RADS TM 4A (3.3%), and Lung-RADS TM 4B, C, X (2.4%). On subsequent LDCT exams, these proportion decreased slightly to 5.2% and 2.2% for Lung-RADS TM 3 and 4A, respectively. Conclusion: Overall implementation of KPWA lung cancer screening suggests an ability to identify eligible patients, engage in shared decision-making, appropriate referral and uptake of LDCT, appropriate use of Lung-RADS TM assessment, and patients who return for follow-up and subsequent annual screening. Opportunities remain for improvement in acceptance of LDCT based on patient needs and further adoption within our system.
by the USPSTF (Table 1, McNemar's odds ratio (OR M)¼11.9, 95%CI 6.8-22.9, p<0.0001). Limited to Blacks, the USPSTF criteria identified 50.8% and the PLCOm2012 identified 74.9%. Only 3 individuals were USPSTF+ve/PLCOm2012-ve and 104 individuals were PLCOm2012+ve/USPSTF-ve (Table 2, OR M ¼34.7, 95%CI 11.5-170.8, p<0.0001). Conclusion: Overall and especially in Blacks, compared to the USPSTF criteria, the PLCOm2012 criteria was significantly more sensitive at identifying lung cancer patients.
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