Gefitinib (ZD-1839) With Concurrent Docetaxel and Conformal Three-Dimensional Thoracic Radiation Followed by Consolidative Docetaxel/Gefitinib for Patients with Stage III NSCLC: A Phase I Study

18165 Background: The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent gefitinib/docetaxel chemotherapy in patients with inoperable stage III NSCLC has not been evaluated. Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily gefitinib (250 mg given orally). Patients recieved concurrent thoracic radiation to a dose of 70 Gy utilizing 3-D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative docetaxel (75 mg/m2) given q 21 days and gefitinib 250 mg p.o. for 1 year or until disease progression. Results: Beginning December 2003, 15 patients have been entered to date to this IRB approved phase I trial to determine the maximum tolerated dose of weekly docetaxel when given concurrent with gefitinib and thoracic radiation. The dose-limiting toxicities (DLT) observed were primarily non-hematologic and occured at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in a grade III dehydration, a second patient experienced grade III diarrhea while a third patient suffered a grade V interstitial pneumonitis, believed to be related to the gefinitib. While 14 of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy, 4 patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent gefitinib/docetaxel thus far appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 docetaxel dose level concurrent with 250 mg of daily gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca. No significant financial relationships to disclose.

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Continuous Infusion of Cilengitide with Radio-Chemotherapy in Stage III Nsclc: a Phase I Study

Annals of Oncology ◽

10.1093/annonc/mdu348.14 ◽

2014 ◽

Vol 25 ◽

pp. iv421

Author(s):

E.L. Cohen-Jonathan Moyal ◽

C. Massabeau ◽

T. Filleron ◽

A. Modesto ◽

J. Bachaud ◽

...

Keyword(s):

Phase I ◽

Continuous Infusion ◽

Phase I Study ◽

Stage Iii ◽

Stage Iii Nsclc ◽

Radio Chemotherapy

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A Phase I Study of Gefitinib with Concurrent Dose-Escalated Weekly Docetaxel and Conformal Three-Dimensional Thoracic Radiation Followed by Consolidative Docetaxel and Maintenance Gefitinib for Patients with Stage III Non-small Cell Lung Cancer

Journal of Thoracic Oncology ◽

10.1097/jto.0b013e3181c59a0e ◽

2010 ◽

Vol 5 (1) ◽

pp. 69-74 ◽

Cited By ~ 24

Author(s):

Brian Center ◽

William Jeffrey Petty ◽

Diandra Ayala ◽

William H. Hinson ◽

James Lovato ◽

...

Keyword(s):

Lung Cancer ◽

Phase I ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Phase I Study ◽

Three Dimensional ◽

Small Cell ◽

Small Cell Lung ◽

Weekly Docetaxel ◽

Thoracic Radiation

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Stage III non small lung cancer (NSCLC): Docetaxel (D), gemcitabine (G), and cisplatin (C) as induction chemotherapy, an Italian phase I study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18201 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18201-18201

Author(s):

S. De Santis ◽

V. Donato ◽

M. R. Migliorino ◽

B. Tedesco ◽

S. Condo ◽

...

Keyword(s):

Phase I ◽

Induction Chemotherapy ◽

Phase Ii ◽

Phase I Study ◽

Objective Response ◽

Stage Iii ◽

Stage Iiia ◽

Phase Ii Studies ◽

Stage Iii Nsclc ◽

Grade 3

18201 Background: Based on the several clinical trials, combined modality therapy became the standard of care for patients with stage III NSCLC “unresectable” with good performance status (Kathy S. Albain, Educational Book ASCO 2006, 453–461; Thomas E. Stinchcombe, Oncologist 2006, 11, 809–823). The most effective induction chemotherapy has yet to be determined. The objective of this prospective phase I study was to define the maximum tolerated dose (MTD), and to evaluate the activity and safety of one of the third generation triplets as a full dose neoadjuvant regimen in patients (pts) with unresectable Stage III NSCLC. Methods: In this study, chemotherapy-naïve pts with stage IIIA-N2 bulky and IIIB (except malignant pleural effusion) NSCLC were eligible. Inclusion into the trial and treatment decisions were done by multidisciplinary panel involving surgeons, medical oncologists and radiotherapists. All drugs were given intravenously on days 1 and 8, and repeated every 3 weeks up to 2 cycles followed by concurrent chemoradiation. D (30–35 mg/m2) was given first, followed by C (35 mg/m2) and G (1000 mg/m2). Results: From Jan ‘06 to Jul ‘06 twelve eligible pts were enrolled, 10/2 m/f gender; median age 63 (50–72), 1 patient with ECOG PS 0, 11 pts with PS 1; 5 pts with stage IIIA-N2 bulky, 7 pts with stage IIIB NSCLC; nine pts were smokers. All pts were evaluable for toxicity. Toxicity grade 3–4 by CTC criteria was: grade 3 neutropenia in 2/3 patients and grade 3 thrombocytopenia in 1/3 patients on the second dose level of chemotherapy (i.e. docetaxel 35 mg/m2), and was considered dose-limiting. Of 9 pts treated at the MTD (i.e. docetaxel 30 mg/m2), only 1 patient developed grade 4 neutropenia and 1 patient grade 3 thrombocytopenia; 3 patients (30%) had grade 2 neutropenia and grade 2 stomatitis. Of 12 evaluable pts for response, after induction chemotherapy eighty-three percent of patients (9/12 pts) had an objective response and 16,6% (2/9 pts) stable disease. Phase II is continuing for larger patient accrual. Conclusions: The recommended doses for further phase II studies are D (30 mg/m2) followed by C (35 mg/m2) and G (1000 mg/m2) every 3 weeks. This regimen is well tolerated and effective, and appears to be an excellent choice for stage III NSCLC. No significant financial relationships to disclose.

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A Phase I Study Demonstrating Manganese Superoxide Dismutase Plasmid Liposome Complex (MnSOD-PL) Reduction of Esophagitis following Standard Chemoradiation in Surgically Unresectable Stage III NSCLC

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2010.07.486 ◽

2010 ◽

Vol 78 (3) ◽

pp. S201

Author(s):

J.S. Greenberger ◽

C.P. Belani ◽

J.D. Leuketich ◽

A. Argiris ◽

S.S. Ramalingam ◽

...

Keyword(s):

Superoxide Dismutase ◽

Phase I ◽

Phase I Study ◽

Manganese Superoxide Dismutase ◽

Stage Iii ◽

Manganese Superoxide ◽

Unresectable Stage ◽

Stage Iii Nsclc

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A phase I/II trial of perioperative paclitaxel (P), carboplatin (C), and erlotinib (E) with concurrent accelerated hyperfractionated radiation (HFRT) followed by maintenance E for stage III non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7557 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7557-7557

Author(s):

N. A. Pennell ◽

G. M. Videtic ◽

S. Murthy ◽

D. Mason ◽

T. W. Rice ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Pathologic Complete Response ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Stage Iii ◽

Stage Iiia ◽

Open Label ◽

Thoracic Radiation ◽

Stage Iii Nsclc

7557 Background: Concurrent chemoradiotherapy (CRT) is standard treatment for stage III NSCLC, although the management of resectable patients (pts) remains controversial. We report an open-label phase I/II trial of the epidermal growth factor receptor inhibitor E added to perioperative CRT for resectable stage III NSCLC pts, followed by maintenance (m) E. Methods: Eligible pts had stage IIIA/B NSCLC, PS 0–1, and were resectable as determined by a thoracic surgeon. Pts received weekly P (50 mg/m2), and C (AUC 2) with daily oral E for 28 days concurrent with twice daily thoracic radiation (1.5 Gy/fraction) to 30 Gy, followed by restaging. Non-progressors underwent resection followed by the same CRT regimen and 2 years of mE (150mg). The primary endpoint of the phase I portion was the maximum tolerated dose (MTD) of E given with CRT; and for the phase II was safety and tolerability. Secondary endpoints were pathologic complete response (pCR) rate, pathologic downstaging of mediastinal nodes, progression free survival (PFS), and overall survival (OS). Results: 9 pts were enrolled in the phase I trial. The MTD of E was150mg, which was the phase II dose used. 25 pts were treated in the phase II component: median age 60, 92% stage IIIA, 64% female, 72% PS 0, 64% adenocarcinoma, and 16% never smokers. The median duration of mE was 5.5 months, with the most common reason for discontinuation being pt preference. There was no grade 4 toxicity. Grade 3 toxicity seen in >5% of pts: rash (12%), diarrhea (9%), nausea (9%), and encephalopathy (6%). The most common toxicities during mE: grade 1/2 diarrhea (72%), rash (61%), fatigue (56%), nausea (22%), and dry eyes (17%).1 pt (4%) had a pCR after neoadjuvant CRT, and 46% were downstaged to pN0–1 at surgery. At a median follow-up of 36.5 mos the median PFS is 41.8 mos (95% CI 9.3-not yet reached). The median OS has not been reached. 3 year survival is 69%. Pts downstaged to pN0–1 vs those with persistent pN2–3 had a median PFS of 41.8 vs 18.1 mos (p=0.11). Conclusions: Perioperative P, C, and E given concurrently with HFRT was well tolerated and showed promising efficacy, while compliance was poor with maintenance E. [Table: see text]

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