- Email: [email protected]
P-447 Treatment of non-small-cell lung cancer with gefitinib (IRESSA)in a compassionate-use program: The Portuguese experience
Posters/Non-smafl ceil lung c a n c e r - Advanced disease ill/B/IV) based sequential approach could allow tbe addition of a 3 ra active agent. while minimizing tmdcit]os, we conducted a phase I tnal. then combined G (300mg/M 2 on days 1. 6. & 15) with P 70mg/M 2 (days 1. 6. & 15). and C (AUC = 5 on day 2) as a 28 day cycle. Twenty eilgJblo, ambulatory patients (Pts) with stage IV NSCLC (9M/11F) wore entered between 3/02 and 11/03. One M Pt never received any therapy, and 19 Pts received a median of 3 courses (range 1 to 8). Eight Pts (42%) achtevod a partial response (PR); 2 achtevod stable disease for 4 and 8 months; 6 had progressive disease; and 3 were removed from study (1 for MI. 1 for multiple PE's. and 1 for rapidly declining performance) Three of the Pts with PR underwent supplemental RT for residual localized disease Five Pts (all PR's) remain alive @ 14+ to 32+ months The median duration of survival is 10 months (range 1 to 32+). and 8, (42%) Pts were alive at one year Toxicity was manageable The current regimen is well tolerated, but offers no large advantage to justify the complos treatroent schedule (Supported in part by NCI~A-SP30 CA72720) Weekly docataxel (TXT) and clsplatin (CIS) for chemonalve
patients (Pts) with advanced non-small cell lung cancer (NSCLC) J. Aisner. L Geunsch. S Schwarz. L Zheng. C Wojtaszek. S LutTker Cancer Institute of New Jersey, New Brunsv~ck, NJ, USA The doublet combination of TXT and CIS is active for NSCLC. and compares well to other platinum based doublets for response, survival, and tmdcit]es To test whether weekly dosing of the TXT/CIS doublet could reduce toxicity, we gave up to 6 courses of 1XT (35 mg/M 2 dl. 6. & 15) and CIS (25mg/M 2 dl. 6. & 15) on a 2&day cycle. Sixteen eligible, ambulatory Pts (9M/TF) wore so far enrolled between 12/03 and l/0b One is too early for evaluation Six of 1,5 (40%) assessable Pts achieved a partial response. 2 ac~eved stable disease for 3 and 5 months. 3 had progressive disease, and 4 (27%) were removed from study for toxicity before the first re-evaluation (1 for marked reduction in creat]hins clearance: 1 for Gr3 N N and diarrhea: 1 for Gr3 diarrhea, and 1 for Gr3 dyspnea Grade 3 4 tmdcit]os include: diarrhea (2). renal (2). dyspnea (2). nail changes (2). fatigue (1). neuropathy (1) The weekly eembinat]on of TXT/CIS Is feasible and active. Further study Is ongolug to better define the response, survival, and toxJcit]os of this weekly combination. (Supported In part by a grant from AvontJs)
~P~2~ Erlotinlb for good prognosis patients w l ~ untreated, advanced stage NSCLC W Akeday. S Maul. M Meier. F FitTpa~ck Huntsman Cancer Institute, Salt Lake City, Utah, USA
Background: Edot]hib domonstT'ated improved survival in previously treated NSCLC. but did not affect survival In unlzeatod NSCLC when used with concurrent chemotherapy. While several conceivable osplanat]ons for this paradox exist, one potential hypothesis Is edot]nJb may be more effective for patients with loss aggressive tumors (I.e. those still surviving after multiple chemotherapy b-eatmonts). The current thai was designed to evaluate edotJnJb before initial chemotherapy In a population of patients with less aggressive tumors by clinical criteria. Methods: Eligibility criteria included stage IIIB/IV or recurrent NSCLC. no prior chemotherapy for systemic cisease. PS 0 1. weight loss loss than 10%. no supplemental oxygen and no urgent symptoms Patients received edotinib 150mg po/day until objective or symptomatic progression before they were switched to chomctherapy. The 10 endpo~nt was progression free survival after 1st chemotherapy. Results: 15 patients have been accrued. The median ago was 65 and 3 were non-smokers The major toxicit]os were rash (Gr2 in 4). liver (Gr3 in 1) and clarrhea (Gr 1 in 4) 11 have been followed long enough for response evaluation, which identified 2 with PR (7 5 and ,5 ,5 m). 4 with stable (4 5. 4. 4. 2 m) and 5 with progression At progression all patients ware able to start chemotherapy The PFS for edot]hib is 3 m The mean chemo PFS and overall survival have net been reached Conduslons: Although results are preliminary, single agent, oral edotinib appears to yield similar PFS and overall survival relative to chemotherapy with less toxicity. A practical and effective means for selection of responsive patients will be necessary for upfront EGFRI to be successful. ~
Fixed-rate gemcltablne Infusion following clsplatln In patients w l ~ stags IIIB/IV non small cell lung cancer: An exploratory
study J Al~sMartinez R S{]nchez~scribano. S Hem~lndez. P Ammbure Hospital Ruber lntamacional, Madrid, Spain
Background: The combination of cisplatin (C) and gemcitabine (G) is one of the most effective clsplat]n based b-eatmont regimens for advanced lung cancer. However. overall response rates (eRR) and survival are still far from optimal, eRR range from 32% to 41% and 1 year su~val rates vary between 33% and 39% in dfforent studios. One strategy to improve the
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efficacy of known agents like C and G Is to Jnb-oduco medJfK:at]ons In their mode and sequence of administration based on better understanding of pharmacokynetics and molecular interactions between them Fixed-rate prolonged infusion of gemcitabine is being osplored in a vahety of tumors due to the fincing that an optimal saturation of the Ohm/rues convert]og gemcitabine into the aetive metabollte dFdCTP is obtained with a r=ed infusion rate 10m~'m2/mJn. It has also boon shown Jn several Jn vitro systems that the sequence of administration can impact the efficacy of chemotherapeutic agents given in combination Since it has been shown in several models that cisp~atin followed by gemcitabine provides a better result we chose this tTeatroent sequence for our study Methods: Patients with advanced, non resectable, stage IIIB and IV and performance status (PS) 0.1 and 2 are being off, red this protocol consist]og of cisplatin 75 mg/m 2 v~th standard hydration measures on day 1 followed by Gomcltabino 1000mg/m 2 at a r=ed infusion rate of 10m~'m2/min on day 1 and the same Gomcltablno dose and schedule without clsplatJn on day 6 of a • w e e k cycle for up to 6 cycles of chemotherapy A complete tumor evaluation Js performed after the first 3 cycles, unless mandated eadJor because of clinical course. Selected cases with very good tolerance and lack of renal toxicity or peripheral neuropathy can be offered additional treatment with this regimen. Results: We present here the preliminary results of the first 11 patients treated with this regimen after a median follow~Jp of 31 weeks. Demographics: Moan age 60 7" years: 83% male. 17% female Adenocereinoma `50%. epidermoid 25%. ether 2`5% Stage IV 92%. IIIB 8.% ToxicIty: Up to now 7`5 cycles have been given with good tolerability: 1 grade 4 tmdcity (neutrepehia) and 8. grade 3 adverse events (diarrhea. nausea& vomiting (2). anemia, leucepenia. neurepathy, noutTopenia, thrembooftopenia) Efficacy Partial responses: 50%: Stable Disease: 37 5%: Progression: 12 b% Median "13meto Progression: 36 4 weeks Meclan Survival 13me: 46 weeks Conclusions: Good tolerabJl~ and promising efficacy results (Clinical Benefit over 85%) warrant further development of this therapeutic approach
]P~]
Some paUante (pts) with "wet" IIIB non-small cell lung cancer (NSCLC) may not develop distant metastases: A reWospective study
O. Altundag. D. Stewart. C. Stevens. D. I~co. G. Ayors. G. Blumonscholn. D. Karp. W. Hong. E Fossella. R. ZJnner. UmveraIty ot Texas M.D. Anderson Cancer Center, Houston, Texas, USA
Background: NSCLC patients with stage IIIB malignant ploural off~Jsions are considered to be incurable and are b-sated with the same therapy used for stage IV clsease. There are few published data detailing the risk of distant metastases of those patients. Methods: A chart review of all pts b-eared on 15 frstJJne advanced NSCLC studios 1997 to 2003 were identified v~th mJrlmal follow qo of 12 months. Results" Of 575 patients on these l b studios. 37 had cytologically conrrmed malignant pleural effusions without radiographic or dinicel evidence of distant cisease at the time of study entTy Of 37 pts all were evaluable were survival Twenty four were male. 13 were female Median agewas b6 (3,5~77") Pathology was 31 and 6 with adenocarcinoma and large cell uncifferent]ated ca histology respec0vely Median time to progression was 5 5 months (1 5 26 b) and median overall survival was 12 5 months (2,5 47 5) With minimum f/u of 13 months no metastases despite documented local reourrenca Corlmary. lymph node or ploural effusion) was seen In 12/37 (32%) pts; 9/12 who have died. Of those 12 pts. 6/37 (16%) are < 6.5 mos (8.5-17) without distant metastases after local recurrence of whom 3/37 (6%) wore greater than 1 yr and 2/3 < 1 yr are still alive. Conclusions: We present data descrlLxog the nsk of clstant metastases In cytologically proven stage IIIB with malignant effusions. The absence of documented disease in 10/31 patients who died indicates that some of these patients may be dying from local prregression without progressing to distant metastases Since almost 20% of patients no had distant metastases in longtime follow-up local aggressive tTeatment stTatogios might be considered in selected cases to improve the outcome At the time of the meeting there will be a data further evaluating the nek and character of metastatic disease. TiP and OS from matched stage IV eentToIs from each of those stucios
•
]gemcltablne Wdocetaxel e (TXT) e with k prolonged l yinfusion (Pl) or (GEM): A promising ~erapeutlc option In patients with advanced, pret]-eated non-small cell lung cancer (NSCLC). A two stage SIMON designed phase II study
G. AntonellJ. D. Prlolo. P. Collna. F. Vitalo. F. Ferrau'. Dtvtston otMedlcal Oncetogy, Taormma, Italy Background and purpose: Second4ine biweekly administered TXT is commonly used in metastatic NSCLC Recent data suggest, however, that weekly 1XT Js well tolerated with equivalent dose intensity and similar response rate. Based upon the pharmacokinetic notion that GEM works through di and tn phosphate denvattvos, optimally generated through a 10 mg/mq/min dose rate of the drug. we have ut]lised PI of GEM. In order to evaluate the association
Posters I Non-small ceil lung c a n c e r - Advanced disease (I//B/IV)
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of weekly TXT with PI of GEM in term of activity and salety we have started a two stage Simon designed phase II study, planhing to include 36 pts with 6 response and p0-pl value of 0 10 0 30 In tha intadm analysis, the e~pected responses should be two on 18 pts for the study to ba cont]nuad Patfants and method'=: from Apdl 2003 to December 2004. 21 pts with advanced NSCLC were treated with 30 mg/m ~ TXT and 900m~'m 2 GEM as 90' infusion, both on day 1-8 each 21 days. There were 17 males and 4 females; median ape was 62y (range 38-75y); median ECOG PS 1 (range 0-1). Histology was adenocarc~noma (12 pts). squamous carcinoma (5 pt). ca~noma NAS (4 pts). s ~ e e n pts had stage IV disease. 5 lots had stage IIIb. Fourteen pts had synchronous distant metastases The metastat]c sites were: lung-supraclavioular nodes (1 pt). lung~one (4pts). lung~rain (4pts). lung4iveradrenal gland (lpt). in 11 pts the involving sites were int~athoracic (lung bilateral or meciast]nal lymphnedes) All the lots were treated with first-line plat]humbased chemotherapy with two e~coptions (due to advanced age) Results: an amount of 67 cycles were administered (median 3/pt. range 2 6cy) All the lots wore avaluable for tmdcity Ohiy one case of G4 neut]'openia and no major extra hematological side effects were seen. 19/21 pts wore evaluable for response, w~h the following results: PR in 3 pts. SD in 5 pts. PD in 11 lots. In two pts the second cycle is st]ll ongoing. Part]al responses were obtained in 3 pts w ~ the best performanee status, the smallest burden of turnour and a good response at the first line chemotherapy. The criteria for the interim analysis wore met after 12 enrolled pts. w~h two o~nfirmed PR. These results supported the reason to oont]nue the study to the second estimated step Toxc~ty HE] N WBC PLT nauro;]athy asthenia ¢~iarrhoaa Nausea- transarnmi~s fever vumdmg GI GII G III GIV
2
21 3 2 4 2 1
1 2 1
2
7 2
4
2
3 2
5
1
These preliminary data confirm the option to further explore this schedule as a new therapeutic option in II line b r NSCLC pts with adequate PS
P~--4~T Resected solitary adrenal metastasis from non-small cell lung cancer D Aranguren. B Bet. R Marks. S Mandrekar Mayo Clinic Rochester, Rochester, MN, USA Background: It has been well established that curative t]'eatment (resection and/or radation therapy) era solitary brain metastas~s from nor. small eell lung cancer provides long term disease free and c~erall survival benefit. The role of resection of a solitary metastasis to an adrenal gland remains less defined and controversial. We review the Mayo Clinic expenenoe and e~amine factors that may af~ct overall survival or time to progression (TIP) Method,=: A retrospective chart r a v i ~ was performed on all NSCLC patients who had a complete or attempted adrenal rusect]on at Mayo Clinic Rochester from January 1984 to December 2004 Simple summary statist]us wore used to describe our cohort Kaplan Meier methods were used to estimate the distribution of overall survival and T I P Findings: Atotal of 31 patients were identified All had a clagnosis of non-small cell lung caneer. There were 25 men and 6 women w ~ a median age of 53 (range 3~;L78). The finding of adrenal metastasis was made synchronously in 14 (45%) pat]ents and metachroneusly in 17 (55%) pat]onts. Nineteen (61%) pat]ents had a oomplete adrenal resection. Twelve (39%) pat]onts had an incomplete e~clsion or sub,opt]real debulking for palliative purposes. 1,5 (48%) pat]ents reeeived some form of additional therapy (chemotherapy and/or radiat]on). One patient died from oomplicat]ons from surgery. Patients who underwent a complete ~cision had a mecian T I P of 7 months (05%C1:5 18.) and a median survival of 15 months (95%C1: 8. 65) Those patients who had incomplete resection had a mecian TTP of 3 months (9,5%C1: 0 9) and a median survival of 12 months (05%C1:2 32) Notably. there wore ?" (37%) resected patients alive at 3 years (4 synchronous. 3 metachrenous) compared to 1 (8%) patient in the non-resected group (synchronous) Five (26%) resected patients were progression free at three years (3 synchronous. 2 metachrenous) as opposedto only 1 (8%) nor-. resected pat]ont (synchronous). Conclusion: The rusect]on of a solitary adrenal metastas~s appears to be assec~ated with an increase in the median TTP and a slight improvement in median survival as opposed to inoomplete resection. Nonetheless. there does appear to be an increase in the pregress~on free and sur-vival rates at 3 years associated with oDmplete resection of a solitary adrenal metastasis. Given the small number of pat]onts and probable biased selection of those who did proceed to surgery, a prospective tnal would have to be done before any definitive conclusions can be made
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Treatment of non-mall-cell lung cancer with geflUnlb (IRESSA) In a compassionate-use program: The Portuguese experlenca
A Araui ol . M Teixeira 2. A Figueiredo 3. J Correia 4. M Melo5. B Parente B. M. Bornardo 7, H. Queiroga u. F. Barata 3. ltns~tuto Portugues de Oncetog/a, Fbrto, Portuga/, 2Hospta/ Santa Mane, Ust~oa, Portugal, ~Centro Hosp/talar
de Co~rnbra, C~mbra, Portugal, 4Hosptfa/ Egas Mociz, Lisboa, Portugal, ~Hosptal Pul/do Valante, IJsboa, Portugal. e Centro Hospttalar VN Gala, VN Gaia, t~rtugal, 7Hospital Capuchos, lJsboa, Portugal, eHospital San Joao, Porto, Portugal Background: Until now. there have been no treatment options for patients with non small4:ell lung cancer (NSCLC) who have relapsed after seoond line chemotherapy. Gefiinib (IRESSA). an orally active epidermal growth factor receptor tyroslno klnase irlhibltor, has been shown to be effective as ~>seoond line monothorapy in two Phase II tnals (IDEAL [IRESSA Duse Evaluation in Advanced Lung cancer] 1 and 2) [Fukuoka at al. J Clin Onco12003:21:2237 46: Kris at al. JAMA 2003:290:2149 58.] We have carried out a retrospective analysis of pat]ents who received gefrdnib as part of the Expanded Access Programme (EAP) and Named Patient Program (NPP) in Portugal Methods: Pat]ents with locally advanced or metastatic NSCLC who had failed secondqine chemotherapy or for whom no other treatment opt]ons existed were eligible to receive gefilJnib (250 m~'day orally) as part ofthe EAP or NPP Data were collected ret]-ospectlvely from the records of patients enrolled in centers participating in the Portuguese Lung Cancer Study Group (GECP). Objective response (OR; complete [CR] or partJal [PR] response) was evaluated using RECIST and safety assessed using serious or non senous adverse events (SAE~AEs). Results: By December 2004. 9 GECP centers had enrolled 105 pat]onts who had received pefit]nlb for ~>4 weeks, and were oonsldored evaluable for both obje~ve response and safety Demography: male/female. 66/39: mean age. 61 0 years (range 29 86): adenoc~cinoma.tsquamous-cell carcinoma/other histology. C00/22/23: pnor chemotherapy 0/1/2/<2. 7/25/63/10: Eastern Cooporative Oncology Group performance status 0 2/<2. 84/21 Mean duration of treatment was 4 2 months (range 1 22 ,5): 38. patients received pefilJnib for <3 months and 36 are still receiving gefiinib Disease control (OR + stable cisease [SD]) was observed in 64 (61 0%) patients: 1 (1 0%) CR. 9 (8 6%) PR and 54 (51.4%) SD. Median overall su~val was 6.6 months. Gefiinib was well tolerated, with the maJonty of non senous AEs being grade 1/2 skin rash. clarrhea, and dry skin. Conclusions: Our retrespect]ve analysis has observed a oomparable disease oDnt]'ol rate (61.0%) to that seen in the IDEAL tnals. Median overall survival was 6.6 months, probably a I~tle more than that expected with best supportive care. reinforcing the need to identify some measurable factors that may guide us in the selection of our patients Gefit]nib was well tolerated in this patient population [P~]
Mlcronudel evaluation of reduction In neoadJuvant chemotherapy related acute toxicity In Locally Aclvance¢l Non Small Cell Lung
Cancer A Bahl S Chandor. I3 Julka. G Rath. D Sharma. A K4Jmar. O Nair ,4//
tn~a Institute of Medical Sciences (AItMS), New Delhi, InCa Background: Lung caneer is the must oommon cancer in the wodd acoount]ng Ibr 17.6% can(ors woddwlde. The aim of the present study was to analyze a reduction in neoadluvant chemotherapy related acute toxicity in locally advanced lung cancer (stage Ilia & III B) using Wobe Mugos E and Es evaluation using micronuolel as a cytopenet]c marker Micronuclei. which are cytoplasmic fragments of DNA. have been used as a biological dosimeter to assess DNA damage Material and Methods: 40 patients of locally advanced NSCLC were randomized into two study arms between 2001 - 2002 One group received neoacquvant chemotherapy using Cisplat]n & Etopuside The other group received necadjuvant chemotherapy using Cisplat]n & Etoposide along with Wobe Mugos E which is a proteolyl]c enzyme preparation. A study of micronuclei fi'eduenoy was done pre & post chemotherapy in both groups. Table: Pre and Post chemotherapy micronuelei frequency (n Mean Mioronuclei fi'ecpJency Group A Group B Pra chemotherapy Post chemotherapy
11 3495 44.8365
12 0340 36.9890
38) p value
0.019
Results: 38. pat]ents were available for final evaluation Mecian ape of presentat]on was 58 ,5 years There were 30 male and 10 ~male patients 1,5 pabents had NSCLC stage IliA while 25 patients had Stage IIIB. Anemia was the most common hematological t~ic~ty observed (seen in 81% of patients) Nausea & vomiting were the must oDmmon non hematological to~aty seen. Wobe Mugos E was Ibund to reduce the inadenco of leuooperla (p = 0.005).
patients (Pts) with advanced non-small cell lung cancer (NSCLC) J. Aisner. L Geunsch. S Schwarz. L Zheng. C Wojtaszek. S LutTker Cancer Institute of New Jersey, New Brunsv~ck, NJ, USA The doublet combination of TXT and CIS is active for NSCLC. and compares well to other platinum based doublets for response, survival, and tmdcit]es To test whether weekly dosing of the TXT/CIS doublet could reduce toxicity, we gave up to 6 courses of 1XT (35 mg/M 2 dl. 6. & 15) and CIS (25mg/M 2 dl. 6. & 15) on a 2&day cycle. Sixteen eligible, ambulatory Pts (9M/TF) wore so far enrolled between 12/03 and l/0b One is too early for evaluation Six of 1,5 (40%) assessable Pts achieved a partial response. 2 ac~eved stable disease for 3 and 5 months. 3 had progressive disease, and 4 (27%) were removed from study for toxicity before the first re-evaluation (1 for marked reduction in creat]hins clearance: 1 for Gr3 N N and diarrhea: 1 for Gr3 diarrhea, and 1 for Gr3 dyspnea Grade 3 4 tmdcit]os include: diarrhea (2). renal (2). dyspnea (2). nail changes (2). fatigue (1). neuropathy (1) The weekly eembinat]on of TXT/CIS Is feasible and active. Further study Is ongolug to better define the response, survival, and toxJcit]os of this weekly combination. (Supported In part by a grant from AvontJs)
~P~2~ Erlotinlb for good prognosis patients w l ~ untreated, advanced stage NSCLC W Akeday. S Maul. M Meier. F FitTpa~ck Huntsman Cancer Institute, Salt Lake City, Utah, USA
Background: Edot]hib domonstT'ated improved survival in previously treated NSCLC. but did not affect survival In unlzeatod NSCLC when used with concurrent chemotherapy. While several conceivable osplanat]ons for this paradox exist, one potential hypothesis Is edot]nJb may be more effective for patients with loss aggressive tumors (I.e. those still surviving after multiple chemotherapy b-eatmonts). The current thai was designed to evaluate edotJnJb before initial chemotherapy In a population of patients with less aggressive tumors by clinical criteria. Methods: Eligibility criteria included stage IIIB/IV or recurrent NSCLC. no prior chemotherapy for systemic cisease. PS 0 1. weight loss loss than 10%. no supplemental oxygen and no urgent symptoms Patients received edotinib 150mg po/day until objective or symptomatic progression before they were switched to chomctherapy. The 10 endpo~nt was progression free survival after 1st chemotherapy. Results: 15 patients have been accrued. The median ago was 65 and 3 were non-smokers The major toxicit]os were rash (Gr2 in 4). liver (Gr3 in 1) and clarrhea (Gr 1 in 4) 11 have been followed long enough for response evaluation, which identified 2 with PR (7 5 and ,5 ,5 m). 4 with stable (4 5. 4. 4. 2 m) and 5 with progression At progression all patients ware able to start chemotherapy The PFS for edot]hib is 3 m The mean chemo PFS and overall survival have net been reached Conduslons: Although results are preliminary, single agent, oral edotinib appears to yield similar PFS and overall survival relative to chemotherapy with less toxicity. A practical and effective means for selection of responsive patients will be necessary for upfront EGFRI to be successful. ~
Fixed-rate gemcltablne Infusion following clsplatln In patients w l ~ stags IIIB/IV non small cell lung cancer: An exploratory
study J Al~sMartinez R S{]nchez~scribano. S Hem~lndez. P Ammbure Hospital Ruber lntamacional, Madrid, Spain
Background: The combination of cisplatin (C) and gemcitabine (G) is one of the most effective clsplat]n based b-eatmont regimens for advanced lung cancer. However. overall response rates (eRR) and survival are still far from optimal, eRR range from 32% to 41% and 1 year su~val rates vary between 33% and 39% in dfforent studios. One strategy to improve the
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efficacy of known agents like C and G Is to Jnb-oduco medJfK:at]ons In their mode and sequence of administration based on better understanding of pharmacokynetics and molecular interactions between them Fixed-rate prolonged infusion of gemcitabine is being osplored in a vahety of tumors due to the fincing that an optimal saturation of the Ohm/rues convert]og gemcitabine into the aetive metabollte dFdCTP is obtained with a r=ed infusion rate 10m~'m2/mJn. It has also boon shown Jn several Jn vitro systems that the sequence of administration can impact the efficacy of chemotherapeutic agents given in combination Since it has been shown in several models that cisp~atin followed by gemcitabine provides a better result we chose this tTeatroent sequence for our study Methods: Patients with advanced, non resectable, stage IIIB and IV and performance status (PS) 0.1 and 2 are being off, red this protocol consist]og of cisplatin 75 mg/m 2 v~th standard hydration measures on day 1 followed by Gomcltabino 1000mg/m 2 at a r=ed infusion rate of 10m~'m2/min on day 1 and the same Gomcltablno dose and schedule without clsplatJn on day 6 of a • w e e k cycle for up to 6 cycles of chemotherapy A complete tumor evaluation Js performed after the first 3 cycles, unless mandated eadJor because of clinical course. Selected cases with very good tolerance and lack of renal toxicity or peripheral neuropathy can be offered additional treatment with this regimen. Results: We present here the preliminary results of the first 11 patients treated with this regimen after a median follow~Jp of 31 weeks. Demographics: Moan age 60 7" years: 83% male. 17% female Adenocereinoma `50%. epidermoid 25%. ether 2`5% Stage IV 92%. IIIB 8.% ToxicIty: Up to now 7`5 cycles have been given with good tolerability: 1 grade 4 tmdcity (neutrepehia) and 8. grade 3 adverse events (diarrhea. nausea& vomiting (2). anemia, leucepenia. neurepathy, noutTopenia, thrembooftopenia) Efficacy Partial responses: 50%: Stable Disease: 37 5%: Progression: 12 b% Median "13meto Progression: 36 4 weeks Meclan Survival 13me: 46 weeks Conclusions: Good tolerabJl~ and promising efficacy results (Clinical Benefit over 85%) warrant further development of this therapeutic approach
]P~]
Some paUante (pts) with "wet" IIIB non-small cell lung cancer (NSCLC) may not develop distant metastases: A reWospective study
O. Altundag. D. Stewart. C. Stevens. D. I~co. G. Ayors. G. Blumonscholn. D. Karp. W. Hong. E Fossella. R. ZJnner. UmveraIty ot Texas M.D. Anderson Cancer Center, Houston, Texas, USA
Background: NSCLC patients with stage IIIB malignant ploural off~Jsions are considered to be incurable and are b-sated with the same therapy used for stage IV clsease. There are few published data detailing the risk of distant metastases of those patients. Methods: A chart review of all pts b-eared on 15 frstJJne advanced NSCLC studios 1997 to 2003 were identified v~th mJrlmal follow qo of 12 months. Results" Of 575 patients on these l b studios. 37 had cytologically conrrmed malignant pleural effusions without radiographic or dinicel evidence of distant cisease at the time of study entTy Of 37 pts all were evaluable were survival Twenty four were male. 13 were female Median agewas b6 (3,5~77") Pathology was 31 and 6 with adenocarcinoma and large cell uncifferent]ated ca histology respec0vely Median time to progression was 5 5 months (1 5 26 b) and median overall survival was 12 5 months (2,5 47 5) With minimum f/u of 13 months no metastases despite documented local reourrenca Corlmary. lymph node or ploural effusion) was seen In 12/37 (32%) pts; 9/12 who have died. Of those 12 pts. 6/37 (16%) are < 6.5 mos (8.5-17) without distant metastases after local recurrence of whom 3/37 (6%) wore greater than 1 yr and 2/3 < 1 yr are still alive. Conclusions: We present data descrlLxog the nsk of clstant metastases In cytologically proven stage IIIB with malignant effusions. The absence of documented disease in 10/31 patients who died indicates that some of these patients may be dying from local prregression without progressing to distant metastases Since almost 20% of patients no had distant metastases in longtime follow-up local aggressive tTeatment stTatogios might be considered in selected cases to improve the outcome At the time of the meeting there will be a data further evaluating the nek and character of metastatic disease. TiP and OS from matched stage IV eentToIs from each of those stucios
•
]gemcltablne Wdocetaxel e (TXT) e with k prolonged l yinfusion (Pl) or (GEM): A promising ~erapeutlc option In patients with advanced, pret]-eated non-small cell lung cancer (NSCLC). A two stage SIMON designed phase II study
G. AntonellJ. D. Prlolo. P. Collna. F. Vitalo. F. Ferrau'. Dtvtston otMedlcal Oncetogy, Taormma, Italy Background and purpose: Second4ine biweekly administered TXT is commonly used in metastatic NSCLC Recent data suggest, however, that weekly 1XT Js well tolerated with equivalent dose intensity and similar response rate. Based upon the pharmacokinetic notion that GEM works through di and tn phosphate denvattvos, optimally generated through a 10 mg/mq/min dose rate of the drug. we have ut]lised PI of GEM. In order to evaluate the association
Posters I Non-small ceil lung c a n c e r - Advanced disease (I//B/IV)
$234
of weekly TXT with PI of GEM in term of activity and salety we have started a two stage Simon designed phase II study, planhing to include 36 pts with 6 response and p0-pl value of 0 10 0 30 In tha intadm analysis, the e~pected responses should be two on 18 pts for the study to ba cont]nuad Patfants and method'=: from Apdl 2003 to December 2004. 21 pts with advanced NSCLC were treated with 30 mg/m ~ TXT and 900m~'m 2 GEM as 90' infusion, both on day 1-8 each 21 days. There were 17 males and 4 females; median ape was 62y (range 38-75y); median ECOG PS 1 (range 0-1). Histology was adenocarc~noma (12 pts). squamous carcinoma (5 pt). ca~noma NAS (4 pts). s ~ e e n pts had stage IV disease. 5 lots had stage IIIb. Fourteen pts had synchronous distant metastases The metastat]c sites were: lung-supraclavioular nodes (1 pt). lung~one (4pts). lung~rain (4pts). lung4iveradrenal gland (lpt). in 11 pts the involving sites were int~athoracic (lung bilateral or meciast]nal lymphnedes) All the lots were treated with first-line plat]humbased chemotherapy with two e~coptions (due to advanced age) Results: an amount of 67 cycles were administered (median 3/pt. range 2 6cy) All the lots wore avaluable for tmdcity Ohiy one case of G4 neut]'openia and no major extra hematological side effects were seen. 19/21 pts wore evaluable for response, w~h the following results: PR in 3 pts. SD in 5 pts. PD in 11 lots. In two pts the second cycle is st]ll ongoing. Part]al responses were obtained in 3 pts w ~ the best performanee status, the smallest burden of turnour and a good response at the first line chemotherapy. The criteria for the interim analysis wore met after 12 enrolled pts. w~h two o~nfirmed PR. These results supported the reason to oont]nue the study to the second estimated step Toxc~ty HE] N WBC PLT nauro;]athy asthenia ¢~iarrhoaa Nausea- transarnmi~s fever vumdmg GI GII G III GIV
2
21 3 2 4 2 1
1 2 1
2
7 2
4
2
3 2
5
1
These preliminary data confirm the option to further explore this schedule as a new therapeutic option in II line b r NSCLC pts with adequate PS
P~--4~T Resected solitary adrenal metastasis from non-small cell lung cancer D Aranguren. B Bet. R Marks. S Mandrekar Mayo Clinic Rochester, Rochester, MN, USA Background: It has been well established that curative t]'eatment (resection and/or radation therapy) era solitary brain metastas~s from nor. small eell lung cancer provides long term disease free and c~erall survival benefit. The role of resection of a solitary metastasis to an adrenal gland remains less defined and controversial. We review the Mayo Clinic expenenoe and e~amine factors that may af~ct overall survival or time to progression (TIP) Method,=: A retrospective chart r a v i ~ was performed on all NSCLC patients who had a complete or attempted adrenal rusect]on at Mayo Clinic Rochester from January 1984 to December 2004 Simple summary statist]us wore used to describe our cohort Kaplan Meier methods were used to estimate the distribution of overall survival and T I P Findings: Atotal of 31 patients were identified All had a clagnosis of non-small cell lung caneer. There were 25 men and 6 women w ~ a median age of 53 (range 3~;L78). The finding of adrenal metastasis was made synchronously in 14 (45%) pat]ents and metachroneusly in 17 (55%) pat]onts. Nineteen (61%) pat]ents had a oomplete adrenal resection. Twelve (39%) pat]onts had an incomplete e~clsion or sub,opt]real debulking for palliative purposes. 1,5 (48%) pat]ents reeeived some form of additional therapy (chemotherapy and/or radiat]on). One patient died from oomplicat]ons from surgery. Patients who underwent a complete ~cision had a mecian T I P of 7 months (05%C1:5 18.) and a median survival of 15 months (95%C1: 8. 65) Those patients who had incomplete resection had a mecian TTP of 3 months (9,5%C1: 0 9) and a median survival of 12 months (05%C1:2 32) Notably. there wore ?" (37%) resected patients alive at 3 years (4 synchronous. 3 metachrenous) compared to 1 (8%) patient in the non-resected group (synchronous) Five (26%) resected patients were progression free at three years (3 synchronous. 2 metachrenous) as opposedto only 1 (8%) nor-. resected pat]ont (synchronous). Conclusion: The rusect]on of a solitary adrenal metastas~s appears to be assec~ated with an increase in the median TTP and a slight improvement in median survival as opposed to inoomplete resection. Nonetheless. there does appear to be an increase in the pregress~on free and sur-vival rates at 3 years associated with oDmplete resection of a solitary adrenal metastasis. Given the small number of pat]onts and probable biased selection of those who did proceed to surgery, a prospective tnal would have to be done before any definitive conclusions can be made
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Treatment of non-mall-cell lung cancer with geflUnlb (IRESSA) In a compassionate-use program: The Portuguese experlenca
A Araui ol . M Teixeira 2. A Figueiredo 3. J Correia 4. M Melo5. B Parente B. M. Bornardo 7, H. Queiroga u. F. Barata 3. ltns~tuto Portugues de Oncetog/a, Fbrto, Portuga/, 2Hospta/ Santa Mane, Ust~oa, Portugal, ~Centro Hosp/talar
de Co~rnbra, C~mbra, Portugal, 4Hosptfa/ Egas Mociz, Lisboa, Portugal, ~Hosptal Pul/do Valante, IJsboa, Portugal. e Centro Hospttalar VN Gala, VN Gaia, t~rtugal, 7Hospital Capuchos, lJsboa, Portugal, eHospital San Joao, Porto, Portugal Background: Until now. there have been no treatment options for patients with non small4:ell lung cancer (NSCLC) who have relapsed after seoond line chemotherapy. Gefiinib (IRESSA). an orally active epidermal growth factor receptor tyroslno klnase irlhibltor, has been shown to be effective as ~>seoond line monothorapy in two Phase II tnals (IDEAL [IRESSA Duse Evaluation in Advanced Lung cancer] 1 and 2) [Fukuoka at al. J Clin Onco12003:21:2237 46: Kris at al. JAMA 2003:290:2149 58.] We have carried out a retrospective analysis of pat]ents who received gefrdnib as part of the Expanded Access Programme (EAP) and Named Patient Program (NPP) in Portugal Methods: Pat]ents with locally advanced or metastatic NSCLC who had failed secondqine chemotherapy or for whom no other treatment opt]ons existed were eligible to receive gefilJnib (250 m~'day orally) as part ofthe EAP or NPP Data were collected ret]-ospectlvely from the records of patients enrolled in centers participating in the Portuguese Lung Cancer Study Group (GECP). Objective response (OR; complete [CR] or partJal [PR] response) was evaluated using RECIST and safety assessed using serious or non senous adverse events (SAE~AEs). Results: By December 2004. 9 GECP centers had enrolled 105 pat]onts who had received pefit]nlb for ~>4 weeks, and were oonsldored evaluable for both obje~ve response and safety Demography: male/female. 66/39: mean age. 61 0 years (range 29 86): adenoc~cinoma.tsquamous-cell carcinoma/other histology. C00/22/23: pnor chemotherapy 0/1/2/<2. 7/25/63/10: Eastern Cooporative Oncology Group performance status 0 2/<2. 84/21 Mean duration of treatment was 4 2 months (range 1 22 ,5): 38. patients received pefilJnib for <3 months and 36 are still receiving gefiinib Disease control (OR + stable cisease [SD]) was observed in 64 (61 0%) patients: 1 (1 0%) CR. 9 (8 6%) PR and 54 (51.4%) SD. Median overall su~val was 6.6 months. Gefiinib was well tolerated, with the maJonty of non senous AEs being grade 1/2 skin rash. clarrhea, and dry skin. Conclusions: Our retrespect]ve analysis has observed a oomparable disease oDnt]'ol rate (61.0%) to that seen in the IDEAL tnals. Median overall survival was 6.6 months, probably a I~tle more than that expected with best supportive care. reinforcing the need to identify some measurable factors that may guide us in the selection of our patients Gefit]nib was well tolerated in this patient population [P~]
Mlcronudel evaluation of reduction In neoadJuvant chemotherapy related acute toxicity In Locally Aclvance¢l Non Small Cell Lung
Cancer A Bahl S Chandor. I3 Julka. G Rath. D Sharma. A K4Jmar. O Nair ,4//
tn~a Institute of Medical Sciences (AItMS), New Delhi, InCa Background: Lung caneer is the must oommon cancer in the wodd acoount]ng Ibr 17.6% can(ors woddwlde. The aim of the present study was to analyze a reduction in neoadluvant chemotherapy related acute toxicity in locally advanced lung cancer (stage Ilia & III B) using Wobe Mugos E and Es evaluation using micronuolel as a cytopenet]c marker Micronuclei. which are cytoplasmic fragments of DNA. have been used as a biological dosimeter to assess DNA damage Material and Methods: 40 patients of locally advanced NSCLC were randomized into two study arms between 2001 - 2002 One group received neoacquvant chemotherapy using Cisplat]n & Etopuside The other group received necadjuvant chemotherapy using Cisplat]n & Etoposide along with Wobe Mugos E which is a proteolyl]c enzyme preparation. A study of micronuclei fi'eduenoy was done pre & post chemotherapy in both groups. Table: Pre and Post chemotherapy micronuelei frequency (n Mean Mioronuclei fi'ecpJency Group A Group B Pra chemotherapy Post chemotherapy
11 3495 44.8365
12 0340 36.9890
38) p value
0.019
Results: 38. pat]ents were available for final evaluation Mecian ape of presentat]on was 58 ,5 years There were 30 male and 10 ~male patients 1,5 pabents had NSCLC stage IliA while 25 patients had Stage IIIB. Anemia was the most common hematological t~ic~ty observed (seen in 81% of patients) Nausea & vomiting were the must oDmmon non hematological to~aty seen. Wobe Mugos E was Ibund to reduce the inadenco of leuooperla (p = 0.005).