Operator's manual for tractor, full tracked, low speed, DED, medium drawbar pull, SSN M061 : tractor, model D7G, tractor with ripper, NSN 2410-01-223-0350 ... tractor with winch and winterized cab, NSN 2410-01-253-2117.

"20 January 1989."

Unit, direct support, and general support repair parts and special tools list for tractor, model D7G, tractor with ripper, NSN 2410-01-223-0350 ... tractor with winch and winterized cab, NSN 2410-01-253-2117.

"April 1989."

Hand receipt manual covering end item/Components Of End Item (COEI), Basic Issue Items (BII), and Additional Authorization List (AAL) for radio sets, AN/VRC-12 (NSN 5820-00-223-7412) ...

"January 1979."

Operator's and organizational maintenance manual : radio sets AN/VRC-53 (NSN 5820-00-223-7467), AN/VRC-64 (NSN 5820-00-223-7475), AN/GRC-125 (NSN 5820-00-223-7411), and AN/GRC-160 (NSN 5820-00-223-7473), and amplifier-power supply groups OA-3633/GRC and OA-3633A/GRC (NSN 5820-00-973-3383).

Includes index.

Hand receipt technical manual covering end item/Components of End Item (COEI), Basic Issue Items, and Additional Authorization List (AAL) related to radio sets, AN/VRC-12 (NSN 5820-00-223-7412), AN/VRC-43 (NSN 5820-00-223-7415) ... (used with intercom system).

"January 1979."

Organizational maintenance repair parts and special tools list for radio sets AN/VRC-53 (NSN 5820-00-223-7467), AN/VRC-64 (NSN 5820-00-223-7475), AN/GRC-125 (NSN 5820-00-223-7411), and AN/GRC-160 (NSN 5820-00-223-7473), and amplifier, power supply groups OA-3633/GRC and OA-3633A/GRC (parts list for OA-3633/GRC and OA-3633A/GRC (NSN 5820-00-973-3383) only)).

"4 December 1981."

Hand receipt manual covering end item/Components of End Item (COEI), Basic Issue Items (BII), and Additional Authorization List (AAL) for radio sets AN/GRC-106 (NSN 5820-00-402-2263) and AN/GRC-106A (NSN 5820-00-223-7548) LIN Q32756.

"28 November 1978."

Direct support and general support maintenance manual : radio sets AN/VRC-12 (NSN 5820-00-223-7412), AN/VRC-43 (NSN 5820-00-223-7415), AN/VRC-44 (NSN 5820-00-223-7417 ... receiver-transmitters, radio RT-246/VRC ....

"16 April 1984"--Vol. 1.

Direct support and general support maintenance manual : radio sets AN/VRC-12 (NSN 5820-00-223-7412), AN/VRC-44 (NSN 5820-00-223-7417), AN/VRC-47 (NSN 5820-00-223-7434) ... receivers, radio R-442VRC and R-442A/VRC (NSN 5820-00-892-0624).

"16 April 1984."

Operator, organizational, and field maintenance manual : voltmeter, phase angle ME-223/U and North Atlantic Industries models 202R and 202AR.

"August 1962."

Operator's, organizational, direct support, and general support maintenance repair parts and special tools list (including depot maintenance repair parts and special tools list) for multimeter AN/USM-223.

"September 1974."

Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial

BACKGROUND: In the previously reported ALSYMPCA trial in patients with castration-resistant prostate cancer and symptomatic bone metastases, overall survival was significantly longer in patients treated with radium-223 dichloride (radium-223) than in patients treated with placebo. In this study, we investigated safety and overall survival in radium-223 treated patients in an early access programme done after the ALSYMPCA study and before regulatory approval of radium-223.

METHODS: We did an international, prospective, interventional, open-label, single-arm, phase 3b study. Enrolled patients were aged 18 years or older with histologically or cytologically confirmed progressive bone-predominant metastatic castration-resistant prostate cancer with two or more skeletal metastases on imaging (with no restriction as to whether they were symptomatic or asymptomatic; without visceral disease but lymph node metastases were allowed). Patients received intravenous injections of radium-223, 50 kBq/kg (current recommendation 55 kBq/kg after implementation of National Institute of Standards and Technology update on April 18, 2016) every 4 weeks for up to six injections. Other concomitant anticancer therapies were allowed. Primary endpoints were safety and overall survival. The safety and efficacy analyses were done on all patients who received at least one dose of the study drug. The study has been completed, and we report the final analysis here. This study is registered with ClinicalTrials.gov, number NCT01618370, and the European Union Clinical Trials Register, EudraCT number 2012-000075-16.

FINDINGS: Between July 22, 2012, and Dec 19, 2013, 839 patients were enrolled from 113 sites in 14 countries. 696 patients received one or more doses of radium-223; 403 (58%) of these patients had all six planned injections. Any-grade treatment-emergent adverse events occurred in 523 (75%) of 696 patients; any-grade treatment-emergent adverse events deemed to be related to treatment were reported in 281 (40%) patients. The most common grade 3 or worse treatment-related treatment-emergent adverse events were anaemia in 32 (5%) patients, thrombocytopenia in 15 (2%) patients, neutropenia in ten (1%) patients, and leucopenia in nine (1%) patients. Any grade of serious adverse events were reported in 243 (35%) patients. Median follow-up was 7·5 months (IQR 5-11) and 210 deaths were reported; median overall survival was 16 months (95% CI 13-not available [NA]). In an exploratory analysis of overall survival with predefined factors, median overall survival was longer for: patients with baseline alkaline phosphatase concentration less than the upper limit of normal (ULN; median NA, 95% CI 16 months-NA) than for patients with an alkaline phosphatase concentration equal to or greater than the ULN (median 12 months, 11-15); patients with baseline haemoglobin levels 10 g/dL or greater (median 17 months, 14-NA) than for patients with haemoglobin levels less than 10 g/dL (median 10 months, 8-14); patients with a baseline Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (median NA, 17 months-NA) than for patients with an ECOG PS of 1 (median 13 months, 11-NA) or an ECOG PS of 2 or more (median 7 months, 5-11); and for patients with no reported baseline pain (median NA, 16 months-NA) than for those with mild pain (median 14 months, 13-NA) or moderate-severe pain (median 11 months, 9-13). Median overall survival was also longer in patients who received radium-223 plus abiraterone, enzalutamide, or both (median NA, 95% CI 16 months-NA) than in those who did not receive these agents (median 13 months, 12-16), and in patients who received radium-223 plus denosumab (median NA, 15 months-NA) than in patients who received radium-223 without denosumab (median 13 months, 12-NA).

INTERPRETATION: Our findings show that radium-223 can be safely combined with abiraterone or enzalutamide, which are now both part of the standard of care for patients with metastatic castration-resistant prostate cancer. Furthermore, our findings extend to patients who were asymptomatic at baseline, unlike those enrolled in the pivotal ALSYMPCA study. The findings of prolonged survival in patients treated with concomitant abiraterone, enzalutamide, or denosumab require confirmation in prospective randomised trials.

FUNDING: Pharmaceutical Division of Bayer.

Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial

Background: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.

Objective: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.

Design, setting, and participants: Nine hundred and twenty one patients enrolled at 136 centers globally.

Intervention: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.

Outcome measurements and statistical analysis: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.

Results and limitations: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0–1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2–3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.52–0.93; p = 0.013) and opioid (HR = 0.68; 95% CI: 0.54–0.86; p = 0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR = 0.56, 95% CI: 0.39–0.82, p = 0.002; opioid subgroup: HR = 0.72, 95% CI: 0.53–0.98, p = 0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR = 0.62, 95% CI: 0.46–0.85,p = 0.002). Adverse event incidences were similar between opioid subgroups.

Conclusions: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.

Patient summary: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.