Elderly Non-small Cell Lung Cancer Pts Research Articles

1025P DOcetaxel (DOC) plus RAmucirumab (RAM) with pegylated Granulocyte-colONy stimulating factor (PEG-G-CSF) for elderly patients with advanced non-small cell lung cancer (NSCLC): A phase II trial (DRAGON study: WJOG9416L)

DOC monotherapy is an optional Japanese standard of care for chemo-naïve elderly patients (pts) with advanced NSCLC. DOC+RAM showed superior survival benefit over DOC in second-line for NSCLC. A Japanese phase II study comparing DOC+RAM and DOC showed febrile neutropenia (FN) incidence of one-third in DOC+RAM. DOC+RAM could be a promising candidate for elderly NSCLC pts, but such high FN incidence is a critical concern. We thus adopted a routine primary prophylactic PEG-G-CSF to reduce FN and maximize the efficacy of DOC+RAM in elderly pts.

Bevacizumab (Bv) in non small cell lung cancer (NSCLC) patients ≥75 years old with pre-existing cardiovascular disease (CVD): Experience at a tertiary referral center.

e19087 Background: Bv is a novel anti-angiogenic agent used in many advanced solid tumours, including non-squamous NSCLC. In contrast to clinical studies where enrolled pts are fit, many elderly NSCLC pts suffer from co-morbidities and often have history of a CVD. Methods: Medical records of 2,672 pts diagnosed with NSCLC between 2001-2012 were screened. We identified and examined pts ≥75 yrs old treated with Bv, for their demographics, clinical data and treatment (Tx) details. We focused on those elderly pts with stable pre-existing cardiovascular disease. Results: 356/2672 NSCLC pts received Bv at any Tx line. 33/356 (9.2%) were ≥75 yrs old. Of those, 29 had various co-morbidities including 19 pts with stable CVD on medical Tx. In the 19 pts with CVD the male:female ratio was 17:2 and median age 76 yrs (range 75-86). 8/19 pts had impaired renal function. All pts were of Performance Status ECOG 0/1. Median number of Bv cycles was 5 (range 2-11). 17/19 pts experienced ≥1 side effects (11 epistaxis and haemoptysis, 5 proteinuria, 4 hypertension) which led to treatment discontinuation in 5 pts. No major/fatal adverse events were noted. 8/19 pts (42%) showed radiological partial response and 5 (19%) stable disease (total disease control rate 61%). Median survival from initiation of Bv till death/last follow up was 7 months (range 2-28, 95% CI 5.14-12.55). Conclusions: Treatment with Bevacizumab seems to be safe and effective in elderly NSCLC patients with controlled pre-existing cardiovascular disease and good PS. These patients might benefit from participation in clinical trials similarly to younger NSCLC patients.

1301P - Final Analysis of Randomized Phase II Trial of Carboplatin Combined with Weekly Paclitaxel (CP) and Docetaxel Alone (D) in Elderly Patients (PTS) with Advanced Non-Small Cell Lung Cancer (NSCLC): NJLCG 0801

ABSTRACT Background Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine. D has been considered as an alternative option for this population in Japan (WJTOG9904, JCO 2006). Meanwhile, we have shown the high efficacy of CP for elderly pts (NJLCG0403, Ann Oncol 2010). Thus we compared the two regimens to select a proper candidate for future phase III trial. Methods Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m2 on day 1, 8, and 15) every 4 weeks or D (60mg/m2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 54% (95%CI: 39-69%) and 24% (95%CI: 11-37%) in the CP and D arm, respectively. With a median follow-up of 27.6 months, median PFS were 6.6 and 3.5 months in the CP and D arm, respectively (P = 0.0005) and median survival time were 14.3 and 13.8 months in the CP and D arm, respectively (P = 0.24). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm. Conclusions The platinum doublet CP achieved higher activity with less toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011). Disclosure M. Maemondo: Makoto Maemondo receives honoraria from Sanofi. S. Sugawara: Shunichi Sugawara receives honoraria from Sanofi. A. Inoue: Akira Inoue receives honoraria from Sanofi. All other authors have declared no conflicts of interest.

1282P - Topical: Randomized Phase III Trial of Erlotinib Compared with Placebo in Patients with Advanced Non–Small Cell Lung Cancer (NSCLC) Unsuitable for First-Line Chemotherapy: Updated Analysis

ABSTRACT Background Despite the recommendation to treat advanced NSCLC with platinum-based chemotherapy, the majority of these pts receive only active supportive care (ASC) because of poor performance or multiple co-morbidities. We previously showed that erlotinib significantly improved PFS in such patients, but with an enhanced OS and PFS effect in female pts. Here, we report mature OS data including the association of first-cycle rash (FCR). Methods 670 pts with stage IIIB/IV NSCLC (ECOG PS 2/3 or PS 0/1 with multiple co-morbidities unsuitable for chemotherapy) were randomized to receive placebo (n = 320) or erlotinib 150 mg/day (n = 350) and ASC until disease progression/toxicity. OS, PFS, adverse events, and QoL were examined. Pre-specified subgroup analyses included erlotinib-rash ≤28 days of starting treatment (FCR), and EGFR where available. Results Baseline characteristics were well balanced in these predominantly elderly NSCLC pts (median = 77 yrs, range 42-91). Among all pts, the hazard ratios (HRs) were 0.94 (95% CI 0.81-1.10, P = 0.46) for OS. Pts receiving erlotinib had a better PFS, HR = 0.83 (95% CI 0.71-0.97, P = 0.02). 59% of pts on erlotinib developed FCR. FCR was the only independent factor predictive of OS (HR = 0.17; P = 0.02) in a multivariate analysis containing rash, age, gender, histology, ECOG score and stage. There was a benefit for both OS (HR = 0.76, 95% CI 0.63-0.92, P = 0.01) and PFS (HR = 0.66, CI 0.54-0.80, P Conclusions Erlotinib prolongs PFS and OS in patients with advanced NSCLC considered unsuitable for chemotherapy, but only if they develop FCR. Disclosure All authors have declared no conflicts of interest.

Randomized phase II trial of carboplatin combined with weekly paclitaxel (CP) and docetaxel alone (D) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): NJLCG 0801.

7565 Background: Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine globally. However, we have demonstrated the high efficacy of CP for elderly pts in our previous trial (Ann Oncol 2010). Meanwhile, D has been considered as an alternative option for this population in Japan according to the result of WJTOG9904 (JCO 2006). Thus we compared the two regimens to select the proper candidate for future phase III trial. Methods: Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m2 on day 1, 8, and 15) every 4 weeks or D (60mg/m2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results: Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 51% (95%CI: 36-66%) and 26% (95%CI: 12-39%) in the CP and D arm, respectively. With a median follow-up of 18.4 months, median PFS were 6.5 and 3.9 months in the CP and D arm, respectively (Logrank, P=0.0027). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm but none in CP arm. Conclusions: The platinum doublet CP achieved higher activity with an acceptable toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011).

A multicenter phase II randomized study of gemcitabine (G) weekly followed by erlotinib (E) after progression versus E followed by G after progression in advanced non-small cell lung cancer (NSCLC) in vulnerable elderly patients selected with a comprehensive geriatric assessment (CGA) (GFPC*0505).

e18002 Background: Elderly patients (pts) are a heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of weekly G followed by E after progression versus E following by G after progression in vulnerable elderly advanced NSCLC patients selected on the basis of a CGA and Charlson score (CS). Methods: This multicenter phase II study randomized chemonaive pts with stage IV and IIIB with pleural effusion received G 1,250mg/m2 days 1, 8, for a maximum of 18 weeks or until progression, followed by E until second progression (arm A) versus E in first line followed by G until second progression (arm B).Only vulnerable pts (without dependence for ADL and geriatric syndrome) selected by CGA using a software (EGSK) included in a palm assistant with 10 items: socio-economic conditions, cognitive assessment, depression scale, nutritional risk, quality of life(QOL), ADL, IADL (Lawton), incontinence, falls, pain. Major endpoint was time to second progression (TTP2), secondary endpoints were response, time to first progression (TTP1), safety, QOL. Results: 95 pts (67 available today) were enrolled from Aug 2006 to Dec 2009. Patients: Male/Female 54/13, median age 78.1; PS 0/1/2:22/33/10, median co-morbidity (CS) 1.85 (1-3), median IADL score 3.48 (1-4), median global geriatric index: 17.7/20. Respectively for arm A and B, partial response was 18% and 7%, stable disease 18% and 27%, progressive disease 64% and 67%,TTP1 81 and 63 days, median survival 4.3 and 3.9 months. The main WHO grade 3/4 toxicity was anemia 12.5% and fatigue 12.5% in arm A and fatigue 28.6% and anemia 5.7% in B. Conclusions: Preliminary analysis suggests that either the G followed by E or E followed by G appears to have acceptable toxicity but moderate activity, comparable in terms of efficacy to prior data in this vulnerable elderly NSCLC pts population with significant co-morbidities. Our trial confirms the necessity to identify the better tools in CGA to distinguish frail pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Boehringer Ingelheim, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Roche

A multicenter phase II randomized study of docetaxel (D)/gemcitabine (G) weekly followed by erlotinib (E) after progression versus erlotinib followed by docetaxel/gemcitabine after progression in advanced non-small cell lung cancer (NSCLC) in fit elderly patients selected with a comprehensive geriatric assessment (CGA): Groupe Français de Pneumocancerologie (GFPC)*0504.

7536 Background: Elderly pts is an heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of weekly D/G followed by E after progression versus E following by D + G after progression in fit elderly advanced NSCLC patients selected on the basis of a CGA and Charlson score. Methods: This multicenter phase II study randomized chemonaive pts with stage IV and IIIB with pleural effusion received D 30 mg/m2 weekly for 6 consecutive weeks (wks) plus G 900 mg/m2 days 1, 8, 22, 29 followed by 2 wks off, for a maximum of 24 wks or until progression, followed by E until second progression (arm A) versus E in first line followed by D+G until second progression (arm B). Only fit pts (without dependence for ADL or IADL and geriatric syndrom) selected by CGA using a software (EGSK) included in a palm assistant with 10 items: socio-economic conditions, cognitive assessment,depression scale, nutritional risk, quality of life (QOL), ADL, IADL, incontinence, falls, pain. Major endpoint was time to second progression (TTP2), secondary endpoints were response, time to first progression (TTP1), safety, QOL. Results: 100 pts (99 available) were enrolled from July 2006 to November 2008. Patients: Male/Female 59/40, median age 75.9; PS 0/1/2:43/49/6, median comorbidity 0, 4 (0-4) median global geriatric index: 18.5/20. Respectively for arm A and B: partial response was 26.3% and 18.8%, stable disease 42.1% and 33.3%, progressive disease 31.6% and 47.9%,TTP1: 4.7 and 3.1 months, TTP2: 7.7 and 6.6 months, median survival 9.4 and 7.1 months. The main WHO grade 3/4 toxicity was neutropenia 29.2% and fatigue 10.4% in arm A and fatigue 11.8% and cutaneous 11.8% in B. Conclusions: Preliminary analysis suggests that either the combination of weekly D and G followed by E or E followed by D+G appears to be promising with a favourable toxicity profile in fit elderly NSCLC pts with mild comorbidity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Boehringer Ingelheim, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Pfizer, Roche, sanofi-aventis

Cetuximab (C) and gemcitabine (G) in elderly or adult PS2 advanced non small-cell lung cancer (NSCLC) patients (pts): The CALC1 randomised phase II trials

8117 Background: The optimal way of adding anti-EGFR antibodies to chemotherapy in the first line treatment of advanced NSCLC is unknown. We performed two parallel randomised phase 2 studies, one with elderly (CALC1-E) and one with adult performance status 2 (CALC1-PS2) pts, to choose a combined or a sequential strategy of G+C for phase 3 trials. Definitive results of CALC1-E are reported. Methods: Stage IV or IIIb (with supraclavear nodes or pleural effusion) NSCLC pts, aged 70+ with PS 0–2 for CALC1-E or aged <70 with PS2 for CALC1-PS2, were eligible. Pts were randomised to combination (G, 1200 mg/m2 dd 1 & 8 q 21 max 6 cycles, plus C, 400 mg/m2 d1 then 250 mg/m2 weekly until progression) or sequential (G as above followed, after progression or 6 cycles, by C as above) strategy. A selection design was applied with rate of pts alive at 1 year as primary end-point; 58 elderly and 42 PS2 pts were required. Results: 29 elderly pts were randomly assigned to each arm from Nov 05 to Jun 06; median age 74 (70–81), 74% males, 88% PS 0–1. In the sequential arm, 10 patients (34.5%) were not able to receive C after G. At 1 year, 12 pts (41.4%) were alive in the combination and 9 (31.0%) in the sequential arm; with the combination, median survival of 20 patients with grade 1–3 skin toxicity was 54 weeks vs 10 weeks in 9 patients with grade 0. Overall toxicity was similar in the two arms. There were 4 early deaths possibly due to treatment, 2 in each arm. Progression-free survival and response rate were similar in the two arms. Conclusions: In elderly NSCLC pts, the optimal way of adding C to G is combination. A phase 3 trial is being planned to verify whether the addition of C does prolong survival in this clinical setting. Data of CALC1-PS2 will be available in March 2008. ClinicalTrials.gov ID: NCT00330746. Partially supported by Merck- Pharma Spa, Italy. No significant financial relationships to disclose.

Can baseline complete geriatric assessment (CGA) predict toxicity in elderly non-small cell lung cancer (NSCLC) patients (pts) receiving combination chemotherapy? Results from the first 100 pts in the prospective multicenter NVALT-3 study

7537 Background: Nearly 50% of NSCLC pts are aged over 70 years, but only few receive combination chemotherapy. Undertreatment results from a fear of associated toxicities. CGA may predict which patients are prone to toxicities, and thus allow patient selection for such treatment. Methods: A total of 182 NSCLC pts = 70 years with stage IIIb/IV disease were randomized to 4 cycles carboplatin/gemcitabine (group 1) or carboplatin/paclitaxel (group 2). Before treatment, CGA was performed using the following instruments: WHO Performance Scale (PS), Charlson comorbidity index (CCI), Cumulative Illness Rating Scale-Geriatrics (CIRS-G), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Timed “Up&amp;Go” (TUG), Mini-Mental State Examination (MMSE), Geriatric Depression Score (GDS-15), Groningen Frailty Indicator (GFI). Toxicity was scored using NCI-CTC v2. Toxicity related outcomes were defined as all grade III/IV toxicities, toxicity related SAEs, = grade II neurological toxicity and the ability to finish all cycles. Results: In the first 100 pts mean age was 75 yrs (range 70–85). PS was 0 in 30%, 1 in 56% and 2 in 14%. 57% completed all 4 cycles. 11% stopped treatment prematurely due to toxicity and 12% due to PD. Overall, grade III/IV toxicity occurred in 66% of pts, toxicity related SAEs in 12%, and 35% experienced = grade 2 neurological toxicity (n=13 group 1, n=22 group 2). Median (range) baseline CGA scores were as follows: CCI 1.0 (0–7), CIRS-G 3.0 (0–14), ADL independent 72%, IADL independent 50%, TUG 12.0 sec.(5–40), MMSE 29 (19–30), GDS-15 normal (score 0–4) 71%, GFI 3.0 (0–10). Multivariate logistic regression indicated that, for experiencing toxicity related SAEs CIRS-G provided extra information, for experiencing neurological toxicities MMSE was predictive and for finishing all cycles, IADL provided extra information in addition to PS and stage. Conclusions: CGA can predict toxicity in elderly NSCLC pts receiving combination chemotherapy. Data on all 182 patients will be presented. No significant financial relationships to disclose.

Randomized controlled trial comparing docetaxel (D)-cisplatin (P) combination with D alone in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): JCOG0207

7629 Background: Platinum-based chemotherapy is currently recommended as the standard approach for pts with advanced NSCLC. However prospective clinical trials specifically designed for elderly pts demonstrating the P benefit are still lacking. Therefore, we conducted a phase III trial to determine whether the addition of P to single agent-chemotherapy for elderly NSCLC pts could improve survival. Methods: Eligibility criteria included; chemotherapy-naive; stage III/IV NSCLC; age=70 and PS 0–1. Pts were randomized to receive either DP or D with minimization method balancing site, age (=74/=75) and stage (III/IV), and both regimens were given every 4 weeks. DP comprised D (20 mg/m2) and P (25 mg/m2) iv on days 1, 8, 15. D comprised D (25 mg/m2) iv on the same schedule. Primary endpoint was overall survival (OS). The planned sample size was 115 pts in each arm to provide 80% power to detect 0.667 hazard ratio for DP to D in OS and 2.5% one-sided alpha. Results: Between Apr 2003 and Apr 2006, 126 pts were randomized (D/DP: 63/63). The second planned interim analysis was performed on 112 assessable pts (D/DP:56/56, median age 76, =74/=75: 39/61%, male/female: 77/23%, PS 0/1: 39/61%, III/IV: 30/70%). Maturity of information, defined proportion of interim events to the planned events, was 26% (=49/191). As the one-sided p-value(p=0.00515) of the stratified log-rank test by age and stage was not lower than the critical value for the interim analysis, the formal criterion for stopping the trial failed to meet. However the Data and Safety Monitoring Board recommended study termination and disclosure of the results based on the strong interaction (two-sided p=0.077, hazard ratios [95% C.I.] for =74/=75: 0.23 [0.09–0.62]/0.72 [0.35- 1.49]) that DP may be beneficial for subgroup of age between 70- 74. Major Grade 3–4 toxicities were (%D/DP): neutropenia 4.9/13.1, anemia 1.6/16.4, anorexia 8.3/24.2, infection 11.7/8.1, pneumonitis 1.7/1.6. TRD occurred in 1 pt in DP arm. Conclusions: The interpretation of study results is limited due to early stopping and resultant loss of statistical power. But these data indicated that =74 young elderly have no more need to evaluate tolerability and efficacy of P. No significant financial relationships to disclose.

The Four-Arm Cooperative Study (FACS) for advanced non-small cell lung cancer (NSCLC): A subgroup analysis in elderly patients (pts)

7115 Background: Efficacy and safety in fit, elderly NSCLC pts receiving platinum-based treatment have been reported to be similar to those in younger pts. However, there is controversy about which platinum-based regimens are suitable for the elderly. To compare efficacy and safety of platinum-based chemotherapy regimens in the elderly, we conducted an age specific subgroup analysis on FACS, a phase III randomized trial comparing four platinum-based regimens for advanced NSCLC. Methods: FACS was designed to compare three platinum-based combination regimens to cisplatin (80 mg/m2, day 1) plus irinotecan (60 mg/m2, days 1, 8, 15) (IP) as the reference arm. The experimental regimens were: carboplatin (AUC 6, day 1) plus paclitaxel (200 mg/m2, day 1) (TC); cisplatin (80 mg/m2, day 1) plus gemcitabine (1000 mg/m2, days 1, 8) (GP); cisplatin (80 mg/m2, day 1) plus vinorelbine (25 mg/m2, days 1,8) (NP). Results: Of the 105 pts ≥ 70 years (17% of 602 enrolled pts), 27 were on the IP arm, 27 on TC, 28 on GP, and 22 on NP. Patient characteristics were similar in each arm. Response rates were 26% in IP, 20% in TC, 32% in GP, 50% in NP. Frequency of grade 3 or greater leukocytopenia (IP/TC/GP/NP: 52%/33%/36%/86%) was higher in NP, and thrombocytopenia (IP/TC/GP/NP: 11%/19%/43%/0%) was higher in GP, however anemia (IP/TC/GP/NP: 56%/19%/29%/55%) was lower in TC and GP. Frequency of grade 2 or greater vomiting (IP/TC/GP/NP: 52%/22%/39%/41%) was lower in TC, and diarrhea (IP/TC/GP/NP: 48%/7%/4%/14%) was lower in TC, GP and NP, however, grade 2 or greater sensory neuropathy (IP/TC/GP/NP: 0%/22%/0%/0%) was higher in TC. One year survival rates were 48% for the IP arm, 48% for TC, 61% for GP, and 46% for NP. There were no significant survival differences between IP and each experimental regimen. In addition, no significant differences between ≥ 70 and &lt; 70 years were observed in each treatment regimen regarding hematological and non-hematological toxicities, response rates, and survival, except that grade 3 or greater anemia was significantly higher in ≥ 70 years pts in IP and NP arms. Conclusions: These platinum-based four regimens were similarly active and tolerable for fit, elderly NSCLC pts, and their efficacy and toxicity in the elderly were similar to those in younger pts. No significant financial relationships to disclose.

A phase II study of vinoreline (VNR) and carboplatin (CBDCA) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)

17108 Background: VNR is one of standard drugs for elderly NSCLC. The role of platinum- based combination chemotherapy for elderly pts is controversial. Methods: Based on our phase I study (Fukuda, et al, abstract 2763, ASCO 2002), we conducted a phase II single arm study of VNR combined with CBDCA for elderly NSCLC pts. Primary endpoints were response and toxicity. Eligibility criteria included: chemotherapy-naïve, good performance status (PS: 0–2), age ≥75, stage IIIB-IV, and adequate hematological, hepatic and renal function, written informed consent. Treatment consisted of VNR 20 mg/m2 i.v. on days 1 and 8 and CBDCA target AUC = 4 (Chatelut formula, Jaffe method) on day 1 of every 4 weeks. Planned sample size was 40. Results: A total of 40 pts were enrolled. Pts characteristics: male/female = 30/10, PS 0/1 = 18/22, median age (range) = 78 (75–86), Ad/Sq/Others = 30/9/1, stage IIIB/IV = 14/26. Forty pts were eligible and assessable for toxicity and survival, and 37 pts were assessable for response on the submission of this abstract. Thirty-three pts were treated with two or more courses of treatment. Overall response rate was 13.5% (95% CI, 4.5%-28.8%); CR= 0, PR= 5, SD = 23, PD = 9. Grade 3 or 4 leukopenia, neutropenia, and anemia were observed in 31.6%, 50.0%, and 7.1%, respectively. Treatment-related death did not occurred. Non-hematological toxicity was mild. The median survival time was 392 days (95% CI, 311–474) and the median time to progression was 114 days. Conclusions: This combination is well-tolerated and modest activity in pts with elderly NSCLC. No significant financial relationships to disclose.

Single agent oral vinorelbine (NVB) in advanced non-small cell lung cancer (NSCLC) in the elderly: Patient benefit improvement by weekly schedule

7120 Background:Single agent IV NVB has proven its effectiveness in elderly NSCLC pts with reduced toxicity. IV and oral NVB formulation have proven comparable bioavailability. This phase II was conducted with oral NVB to evaluate efficacy/tolerability. Methods:Pts to be recruited were ≥70y with unresectable localised or metastatic NSCLC. Oral NVB was given weekly 60mg/m2x3 weeks/1 cy and then escalated to 80mg/m2 if no G4 or no more than 2 G3 neutropenia during 1stcy. At 80mg/m2, if 1 G4 or 2 consecutive G3 neutropenia occurred, dose was reduced to 60mg/m2.Treatment given up to progression. Primary endpoint was response rate (OR) with secondary endpoints being time dependant parameters and clinical benefit evaluation taking into account 6 lung cancer symptoms evaluation by visual analogic scales, weight and PS changes. Results:56 pts were recruited in 11 European centres. Median age was 74y (70–82), 75% were male with a KPS of 80 in 48%, others being 90/100. 43 pts (76.8%) were metastatic at inclusion. Co-morbidities were present in 87.5% of pts with 18% having ≥3. Median dose intensity (DI) was 46.5mg/m2/w with RDI of 65%. 66.7% pts receiving 2d cy were escalated to 80mg/m2. In ITT/evaluable pts, 6 PR (10.7/12.8%) and 25 SD (disease control=55.4/66%) were reported. Response duration was 5.2m, PFS 3.7m and MS 8.2m. 92 doses (73%) were skipped due to haematological toxicity, mostly G3/4 neutropenia in 61cy (30.8%) and leucopenia in 43cy (21.5%); 2 febrile neutropenia were recorded in 1 patient. G3 non-haematological toxicities were fatigue (4%cy), nausea (2.5%cy), diarrhea (1.5%cy). 1 pt had a G4 thrombosis (0.5%). Regarding clinical benefit, improvement was clear for chest pain, cough and dyspnea. Fatigue, appetite and hemoptysis remained stable or slightly decreased. Weight remained stable. On 32 evaluable pts, the clinical benefit response rate was 31.25%. Conclusions:Oral NVB given as a weekly monotherapy was easy to administer and well tolerated, offering an optimal disease control in this elderly NSCLC population leading to a favorable activity /toxicity ratio associated with a clinical benefit. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut de Recherche Pierre Fabre Glaxo Institut de Recherche Pierre Fabre

Single agent oral vinorelbine (NVB) in advanced non-small cell lung cancer (NSCLC) in the elderly: Patient benefit improvement by weekly schedule

7120 Background:Single agent IV NVB has proven its effectiveness in elderly NSCLC pts with reduced toxicity. IV and oral NVB formulation have proven comparable bioavailability. This phase II was conducted with oral NVB to evaluate efficacy/tolerability. Methods:Pts to be recruited were ≥70y with unresectable localised or metastatic NSCLC. Oral NVB was given weekly 60mg/m2x3 weeks/1 cy and then escalated to 80mg/m2 if no G4 or no more than 2 G3 neutropenia during 1stcy. At 80mg/m2, if 1 G4 or 2 consecutive G3 neutropenia occurred, dose was reduced to 60mg/m2.Treatment given up to progression. Primary endpoint was response rate (OR) with secondary endpoints being time dependant parameters and clinical benefit evaluation taking into account 6 lung cancer symptoms evaluation by visual analogic scales, weight and PS changes. Results:56 pts were recruited in 11 European centres. Median age was 74y (70–82), 75% were male with a KPS of 80 in 48%, others being 90/100. 43 pts (76.8%) were metastatic at inclusion. Co-morbidities were present in 87.5% of pts with 18% having ≥3. Median dose intensity (DI) was 46.5mg/m2/w with RDI of 65%. 66.7% pts receiving 2d cy were escalated to 80mg/m2. In ITT/evaluable pts, 6 PR (10.7/12.8%) and 25 SD (disease control=55.4/66%) were reported. Response duration was 5.2m, PFS 3.7m and MS 8.2m. 92 doses (73%) were skipped due to haematological toxicity, mostly G3/4 neutropenia in 61cy (30.8%) and leucopenia in 43cy (21.5%); 2 febrile neutropenia were recorded in 1 patient. G3 non-haematological toxicities were fatigue (4%cy), nausea (2.5%cy), diarrhea (1.5%cy). 1 pt had a G4 thrombosis (0.5%). Regarding clinical benefit, improvement was clear for chest pain, cough and dyspnea. Fatigue, appetite and hemoptysis remained stable or slightly decreased. Weight remained stable. On 32 evaluable pts, the clinical benefit response rate was 31.25%. Conclusions:Oral NVB given as a weekly monotherapy was easy to administer and well tolerated, offering an optimal disease control in this elderly NSCLC population leading to a favorable activity /toxicity ratio associated with a clinical benefit. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut de Recherche Pierre Fabre Glaxo Institut de Recherche Pierre Fabre

A phase II trial of biweekly administration of vinorelbine (V) and gemcitabine (G) in elderly patients (Pts) with advanced non-small cell lung cancer (NSCLC)

7331 Objective: The purpose of this phase II trial was to evaluate the activity and the toxicity in elderly NSCLC pts of biweekly administration of this combination. Pts and Methods: 45 elderly pts with advanced NSCLC were treated with V 25mg/m2 intravenously and G 1000mg/m2 intravenously every 2 weeks. Eligible pts had: age ≥ 70 yrs; measurable or evaluable disease; ECOG PS 0–2; adequate bone marrow, liver and renal function; no previous chemo- or radiotherapy; life expectancy ≥12 weeks; written informed consent. Results: From August 2001 to November 2003, 46 pts were enrolled and 44 pts were eligible: males/females 27/17; median age 76(range 71–84); PS 0/1/2 25/16/3; stage IIIA/IIIB/IV 5/14/25; adeno/squamous 31/13. A total of 194 cycles(median 6/pt, range 1–12) were given. Tumor response and safety were analysed by December 2003. Of the 40 pts evaluable for response, 11(27.5%) had partial response and 19(47.5%) had stable disease. At this writing, median time to progression is 160 days and median survival is 397 days and 21 pts(47.7%) are still alive. All pts were evaluable for toxicity. Toxicity was mild and mainly hematologic. Grade 3/4 toxicities were neutropenia in 35.3/17.6% of pts, leukopenia in 29.4/2.3%, anemia in 0/0% and thrombocytopenia in 0%/2.9%, respectively. 2 pts(4.5%) had febrile neutropenia. Only 5(11.6%) pts had grade 3 or 4 non-hematological toxicities which were mainly constipation. There was one death from sepsis with neutropenia. At 40th Annual Meeting, we will demonstrate the final results of this trial. Conclusions: This VG biweekly schedule shows an acceptable activity in elderly. The toxicity profile is favorable with mild myelotoxicity. No significant financial relationships to disclose.

A phase II trial of biweekly administration of vinorelbine (V) and gemcitabine (G) in elderly patients (Pts) with advanced non-small cell lung cancer (NSCLC)

7331 Objective: The purpose of this phase II trial was to evaluate the activity and the toxicity in elderly NSCLC pts of biweekly administration of this combination. Pts and Methods: 45 elderly pts with advanced NSCLC were treated with V 25mg/m2 intravenously and G 1000mg/m2 intravenously every 2 weeks. Eligible pts had: age ≥ 70 yrs; measurable or evaluable disease; ECOG PS 0–2; adequate bone marrow, liver and renal function; no previous chemo- or radiotherapy; life expectancy ≥12 weeks; written informed consent. Results: From August 2001 to November 2003, 46 pts were enrolled and 44 pts were eligible: males/females 27/17; median age 76(range 71–84); PS 0/1/2 25/16/3; stage IIIA/IIIB/IV 5/14/25; adeno/squamous 31/13. A total of 194 cycles(median 6/pt, range 1–12) were given. Tumor response and safety were analysed by December 2003. Of the 40 pts evaluable for response, 11(27.5%) had partial response and 19(47.5%) had stable disease. At this writing, median time to progression is 160 days and median survival is 397 days and 21 pts(47.7%) are still alive. All pts were evaluable for toxicity. Toxicity was mild and mainly hematologic. Grade 3/4 toxicities were neutropenia in 35.3/17.6% of pts, leukopenia in 29.4/2.3%, anemia in 0/0% and thrombocytopenia in 0%/2.9%, respectively. 2 pts(4.5%) had febrile neutropenia. Only 5(11.6%) pts had grade 3 or 4 non-hematological toxicities which were mainly constipation. There was one death from sepsis with neutropenia. At 40th Annual Meeting, we will demonstrate the final results of this trial. Conclusions: This VG biweekly schedule shows an acceptable activity in elderly. The toxicity profile is favorable with mild myelotoxicity. No significant financial relationships to disclose.