Patient (PT) participation and disaster (D) agency (AG) coordination for oncology (ONC) PT D preparedness (PREP): Analysis of the Great Southern California Shake Out (GSCSO) drill and implications for regional and national emergency (E) planning (P)

e17549 Background: PT E PREP is important (Katrina, Los Angeles fires 2007, 2008). MOASC developed the ONC PT E Network (OPEN) (www.open-central.com; Proc ASCO 2006 a6142, 2007 a17003 , and 2008 a6545). On Novermber 13, 2008, 28 organizations and sponsors (US and Cal govt and private) conducted the GSCSO drill with a Richter scale 7.8 earthquake. MOASC tested OPEN as part of GSCSO. Methods: In OPEN, PTs were given wallet cards with E information (diagnosis, stage, treatment, doses). As part of GSCSO, MOASC a) surveyed two practices in two counties to evaluate ONC PT motivation and PREP; and b) surveyed D AG to determine the triage program for ONC PTs who required CT. PTs in two offices pretended the ONC offices had been closed due to the D. They were asked to call the MOASC E line and advise an address to which they would evacuate where MOASC referred PTs to a participating physician for chemotherapy (CT). Results: 36 PTs participated. In office interviews, PTs had concerns about transportation to evacuation locations during the D, how they would find available phone lines during an E, and whether MOASC lines would be responsive in an E. Only 5 PTs (13.9%) contacted the MOASC E line within 24 hours. The 4 most available D AGs were unaware of how to triage ONC PTs requiring CT, and were unaware of MOASC and ASCO resources. They wanted to refer ONC PTs to E rooms which would be unresponsive to PT needs for CT. Conclusions: ONC PTs are not yet motivated for D PREP (concerns regarding current CT have higher priority). Responding AGs are not capable of correctly triaging ONC PTs for CT. Neither PTs nor doctors have a list of D AGs. State ONC societies, ASCO, and ACCC should create regional E phone response lines through state societies, regional E oncologist contacts, and a single national facilitating D response office, as well as coordinate regional and national D AGs so that PTs can be triaged to appropriate resources. National D AGs funded to coordinate responses should be the source of support for this process. Motivating ONC PTs for EP will require reimbursed practice participation. No significant financial relationships to disclose.

Health care disparity: An analysis of breast, colon, and lung cancer

6579 Background: Lung cancer patients are associated with feeling of guilt about their disease (Schmidt ASCO 2006) and less likely to be referred to specialists (Wassenaar ASCO 2006). They are also commonly affected by smoking related comorbidities. A study was undertaken to evaluate whether treatment differences between lung and other cancers exist. Methods: Public access data for the year 2005 from the National Cancer Data Base (NCDB) was analyzed. Treatment data were categorized by institution (teaching/research [TR] versus community cancer center [CC]) and tumor type (non-small cell lung cancer-NSCLC, breast, colon cancer). Descriptive analysis was performed with student T tests for proportions. Results: The analysis included 18,960 NSCLC patients from a CC and 33,924 from a TR. More patients at TR than CC had surgery: Stage I 65% vs 52% (p < 0.001), Stage II 35% vs 22% (p < 0.001), respectively. The frequency of chemoradiation for stage I and II was higher in CC than TR: stage I 6% vs 3% (p = 0.10), stage II 19% vs 9% (p = 0.004). The frequency of no first course treatment at initial presentation at CC and TR were the following: stage I 15% vs 6%, stage II 18% vs 8%, stage III 21% vs 19%, stage IV 30% vs 24%. For breast and colon cancer, no major differences in no first course treatments were seen between TR and CC in a stage based analysis. More patients with NSCLC (21.2%) did not receive first course treatment in comparison to breast (3.4%, p < 0.001) or colon cancer (7.8%, p < 0.001). These differences were maintained in stage based analysis of the three tumor types. Conclusions: NSCLC patients are at higher risk of not receiving treatment as opposed to those with breast and colon cancer. While medical comorbidities in lung cancer patients may affect these treatment decisions, we noted a higher incidence of no first course treatment in CC than TR centers. For stage I and II, the frequency of no first course treatment in a CC was twice that of a TR. Such institution based differences were not noted in breast and colon cancer. No significant financial relationships to disclose.

Barriers to cancer clinical trials (CCT) participation: “We have met the enemy and he is us.”

6567 Background: A web based survey of attitudes and awareness of cancer survivors (Ca. surv) towards CCT was performed from 3–4, 2005. The survey was developed jointly by the Coalition of Cancer Cooperative Groups and Michigan State University (MSU) and executed by MSU and Knowledge Networks (KN). Methods: Ca surv. were obtained from a panel of 40,000 adults through KN based on a US household probablility sample who agree to weekly surveys in exchange for a free MSN box and ISP service. 2,029 panel members reported a cancer diagnosis (dx); 1,788/2,029 (88%) agreed to participate. Results: About 10% of Ca surv. are aware of CCT opportunities at the time of dx. 73% become aware through a physician (ASCO 2006: 6061). Ca surv. were asked to rank the most trusted sources of health care information from a list of 23 categories on a 0 (least) to 10 (most) scale. Physicians scored the highest (8.6) followed by information from the NCI (8.4) and reports from societies of cancer physicians/researchers (8.3). Although not significantly different from each other, all were significantly different from the other 20 sources (p<.05). CCT aware Ca surv. were asked whether the physician discouraged, was neutral or encouraged participation or made a little, moderate or great deal of effort to educate them and find a CCT. Enrollment (%) was directly related (p< 0.01) to the perceived physician involvement as follows: Encouragement: discouraged (0); neutral (16); encouraged (84); Educate: little (22); moderate (41%); great deal (64%); Find trial: little (23); moderate (39); great deal (82%). Of the 90% of Ca surv. who were not aware of CCT, 65% indicated that they would be somewhat or very receptive to enrollment if they had been made aware of an opportunity. Conclusion: Ca surv. are not CCT averse a priori. The physician is the most trusted, primary source of awareness and influence in decisions concerning CCT. Although there are myriad reported barriers to CCT participation, increased CCT participation hinges upon physician commitment and communication; conversely, a lack thereof may be the greatest barrier to increased CCT participation. No significant financial relationships to disclose.

Correlation of RTOG 9704 (adjuvant therapy (rx) of pancreatic adenocarcinoma (pan ca)) radiation therapy quality assurance scores (RTQASc) with survival (S)

4523 Background: RTOG 9704 demonstrated a marginal S advantage (p=0.054) in multivariate analysis (MVA) of Gemcitabine (G) over 5FU before and after 5FU+RT for patients (pts) with pan ca resected for cure from the pan head but not from non-head sites (ASCO 2006, ASTRO 2006). This analysis was undertaken to assess the impact of RTQASc on S, S by treatment (rx) arm, and toxicity by rx arm. Methods: This is a secondary analysis of a prospective, randomized, phase III trial of the RTOG, ECOG, and SWOG. RTQASc was graded as per protocol (PP) or less than (<) PP. Using prospectively defined guidelines, <PP scores were variation acceptable (VA), variation unacceptable (VU), or incomplete/not evaluable (I/NE). I/NE pts were excluded from further analysis. Toxicities were scored by CTC, v 2.0. S is expressed as median S in yrs. Results: 416 pts had RTQASc of PP (216, 52%) or <PP (200, 48%; 42% VA, 6% VU). Frequency of PP and <PP did not differ by rx arm (PP = 55% on 5FU arm and 48% on G arm). Looking at PP vs <PP frequency of Grade 3+ Heme and Non- Heme toxicity did not vary significantly on the 5FU arm but did show a trend of < toxicity for PP pts on the G arm ( Table ). In contrast, S was increased for all (head, non-head) PP pts (median S 1.74 vs 1.47 yrs, p=0.019) and, in MVA, score of PP significantly impacted on S (p=0.02) but rx arm did not. PP and <PP S curves began to diverge at 14–15 months post surgery. For head pts, in MVA, RTQASc (PP superior to <PP) and rx arm (G superior to 5FU) both correlated with S (p=0.04, p=0.03, respectively). On the G arm PP pts had S of 1.89 yrs, significantly > than S of VA (1.41yrs) and VU (1.37yrs) pts. Conclusions: In this study prospectively defined RTQASc significantly correlated with S and effect of rx arm on S and showed a weaker effect on toxicity (G arm only). Timing of appearance of RTQASc effect on S implies effect on tumor control. In this context failure to consider RTQASc may confound observed outcomes and confuse correct understanding of the importance of RT. [Table: see text] No significant financial relationships to disclose.

Clinical outcomes of 203 adult patients receiving highly (H) and moderately (M) emetogenic (E) chemotherapy (C) following an institutional antiemetic guideline update incorporating aprepitant (A) and palonosetron (P)

19506 Background: A quality improvement project targeted at chemotherapy induced nausea (N) and vomiting (V) was initiated in 2004. The project included an antiemetic guideline update consisting of replacing ASCO 1998 3 tier guidelines with a 4 tier system similar to ASCO 2006. Following implementation of the guidelines an evaluation phase began. Methods: Adult chemotherapy-naïve patients receiving HEC or MEC were asked to participate. HEC patients received P 250 mcg IV each day of chemotherapy, A 125 mg PO day 1 and 80 mg PO days 2 and 3 and dexamethasone (D) 12 mg PO days 1, 2 and 3. MEC patients received P 250 mcg IV and D 12 mg PO on the day of C. Participating patients were asked to complete a 7 question NV tool at least 5 days following C to report on the 5 days following C. Outcomes reported include % of patients without N, % without V and N score using a 0–10 visual analog scale (VAS). Patient satisfaction with the the control of N and V was also assessed using a 0–10 VAS. Results: A total of 151 patients received HEC and 89% and 44% were protected from V and N respectively. A total of 52 patients received MEC and 90% and 56% were protected from V and N respectively The median N score for all patients who reported nausea was 3. The median and mean score for satisfaction with N and V control was 10 and 8.7 respectively. Patient outcomes for the most commonly used C regimens are reported in the table below. Conclusion: Implementation of revised AEG provided patients receiving HEC and MEC a high level of protection from vomiting, low nausea scores and a high level of overall satisfaction with prevention of N and V. Although N scores were low, the incidence of N reported offers an opportunity for further improvement. [Table: see text] No significant financial relationships to disclose.

Quality-of-life (QOL) evaluation for advanced non-small cell lung cancer (NSCLC): Comparison between vinorelbine and gemcitabine followed by docetaxel (VGD), and paclitaxel and carboplatin (PC) regimen on protocol JMTO LC00–03 (BRI LC03- 01)

18043 Background: JMTO LC00–03, a randomized trial of VGD versus PC in patients with advanced NSCLC, showed differences between the two treatment groups in response rate (25 vs 37.1%) and regimens’ specific toxicities including taxane-related toxicities such as numbness (0 vs 16.2%) and neuropathy (0.5 vs 9.6%), but not in overall survival (MST, 13.6 vs 14.1 mos) and progression-free survival (MST, 5.5 vs 5.8 mos). (Kawahara et al, # 7013, ASCO, 2006). Methods: Patients with advanced NSCLC were randomly assigned to VGD or PC. The patients were assessed with Functional Assessment of Cancer Therapy- FACT-L and FACT-Taxane score in baseline, and at 6-, 12-, 18-weeks after the treatment. The longitudinal analysis was used to compare mean changes of the QOL score over the two treatment groups. Results: Sixty-eight patients from the trial (VGD: 34, PC: 34) who submitted both baseline questionnaire and at least one questionnaire over the course of the treatment were subjects of the study. The table presents the estimated changes in mean scores in treatment arms over the time period. The longitudinal analysis showed significant difference in FACT-Taxane (p<0.001) in the treatment over time, but no significant difference in the FACT-L score (p=0.261). The analysis assuming non-random missing mechanism resulted in slightly larger differences in the mean change. Conclusions: There was no statistically significant difference in FACT-L between the two groups, but VGD group was numerically better than PC group at any point from baseline. The significant difference in FACT-Taxane score favoring VGD would be due to the difference in frequency of neuropathy with docetaxel than with paclitaxel. [Table: see text] [Table: see text]

A phase II study of mammalian target of rapamycin (mTOR) inhibitor RAD001 plus imatinib mesylate (IM) in patients with previously treated advanced renal carcinoma (RCC)

15600 Background: The serine-threonine kinase mTOR is a valid target for RCC therapy with temsirolimus treatment resulting in improved overall survival in poor-risk patients (Hudes G et al., ASCO 2006). RAD001 is an oral inhibitor of mTOR which has demonstrated activity in RCC at 10mg/day (Amato R et al., ASCO 2006). IM is a tyrosine kinase inhibitor (TKI) of platelet-derived growth factor receptor (PDGFR), a target that may promote angiogenesis and growth of RCC. Combined mTOR and PDGFR inhibition with RAD001 and IM may achieve vertical blockade through the PI3K/AKT pathway. Methods: Eligibility: metastatic clear cell RCC, performance status (PS) 0–2, adequate organ function, and prior treatment with = 1 systemic therapy. Doses were based on a phase I study of the combination in GIST (Van Oosterom AT et al., ASCO 2005): RAD001 2.5 mg p.o. daily and IM 600 mg p.o. daily. Patients were reimaged every 6 weeks. This is a 2-stage phase II study to determine the 3-month progression-free rate. Results: 14 pts have been enrolled. Median age 66 years (51–79). 6 pts PS 0 and 8 pts PS 1. Median number of prior therapies 1.5 (1–4). 12 of 14 patients had prior TKI therapy. Prior therapies included sorafenib (11 pts), interferon (7), sunitinib (3), bevacizumab (2), erlotinib (1), panitumumab (1), high-dose IL-2 (1). Of 10 pts evaluable for the primary endpoint, 3 are progression-free = 3 months. Best response for 9 pts evaluable by RECIST: PR/CR 0, SD 7, PD 2. Most common adverse events in 11 evaluable patients include nausea (8), edema (7), increased creatinine (7), fatigue (7), transaminase elevation (6), thrombocytopenia (5), leukopenia (5), cough (5), diarrhea (5). Grade 3 adverse events include fatigue (3), LE edema, rash, pleural effusion, increased creatinine, abdominal pain, and thrombocytopenia (1 each). There were no grade 4 toxicities. Unique suspected RAD001 toxicities include grade 3 pneumonitis (1) and angioedema (1). Conclusions: The combination of RAD001 and IM has moderate toxicity. This is one of the first studies in RCC patients predominantly pretreated with a TKI. 3 month progression-free rate appears to be a clinically relevant endpoint in this population. [Table: see text]

Study of three weekly nab-paclitaxel regimens in combination with carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC)

7659 Background: We previously reported that 130-nM albumin-bound form of paclitaxel (ABI-007, nab paclitaxel) 225 - 340 mg/m2 and carboplatin AUC of 6 mg/min·ml (C6), both administered on day (d) 1 every 3 weeks (q3w), produced an objective (PR/CR) response rate (ORR) of 27% in first line patients (pts) with NSCLC with median progression-free (PFS) and overall survivals of 6.0 and >10.3 months respectively [Hawkins et al., ASCO, 2006]. Grade 2 and 3 sensory neuropathy (SN) was 36–56%. The aim of the current study was to obtain clinical experience with weekly schedules of nab- paclitaxel in combination with C6 in NSCLC prior to initiating large scale clinical trials. Methods: 75 Pts with previously untreated, stage IIIB or IV NSCLC with measurable disease and a life expectancy of over 12 weeks were recruited into 3 cohorts (n = 25 each) of successive pts and received nab paclitaxel weekly using 3 different regimens (see table ). Results: Patient Characteristics: 75 pts (100% Caucasian; 84% male; median age, 60; performance status score: 0 [16%], 1 [84%]. Accrual was completed in each cohort and serious adverse events reviewed prior to accrual at the next dose level. The primary efficacy endpoints are provided in the table . Grade 3/4 hematologic toxicities were: neutropenia 32%/35%; thrombocytopenia, 19%/11%; anemia, 24%/3%. The most common non- hematologic toxicities (any grade) were fatigue, 48%; SN, 48%; nausea, 37%; alopecia, 40%; and vomiting, 26%. Grade 2 and 3 SN was 12–28%. Graded toxicity data by regimen will be presented. Conclusions: When combined with C6, the ORR was higher and there was less peripheral neuropathy for weekly nab-paclitaxel compared to our previous experience using q3w administration. [Table: see text] [Table: see text]

Vitamin D (vD) deficiency (def) in breast cancer (BC) patients (pts)

11082 Background: Vitamin D metabolism is important for maintaining bone health and perhaps cancer prevention. Prior studies have reported vD def in 88% of brca pts (Lonning et al ASCO 2006 abst 554), and 79% of women (Chlebowski et al ASCO 2006 abst 6) . Methods: In order to determine the frequency of vD def, we studied 41 consecutive brca pts. Levels of vD were correlated with clinical features. Pts were classified as vD def if 25OH D <20, 1.25 diOH D <14, or D3 <20. Insufficiency (ins) of vD was 25OH D 20–29. Results: 8 pts had vD def (19.5%). This was more common in young pts <60 (37.5%) compared to older pts (8%) (p4) in 5/6 pts <60 and 5/7 older pts. vD def did not correlate with bone disease: 25% def in pts without bone disease, 17% in pts with osteopenia, and 17% in pts with osteoporosis. In older pts, vD was normal in 12/14 pts on anastrazole, and in 7/11 pts not on anastrazole, indicating no relation of anastrazole to vD def. Bisphosphonate (bis) usage was slightly higher in older pts (60%) versus younger pts (38%) but not significantly (p<0.2). While only 19% of pts on bis had vD ins or def, 50% of pts not on bis had ins or def vD (p<0.05). Although only 5% of pts on bis had vD def, 30% of pts not taking bis had vD def (p<0.05). Conclusions: In brca pts, vD def is less than reported, but still frequent. All brca pts should be tested for vD periodically. VD def may be less frequent in pts on bis, and confirmatory trials should be performed. VD levels should also be monitored even if pts report taking vD. VD def or ins should be treated and monitored by oncologists. Since vD may be related to cancer incidence, and to bone disease, all brca trials collecting data on bone events, bone density, and second cancers should also report relationship to vD levels in individual study participants. No significant financial relationships to disclose.