This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) and age > or = 70 years who were treated with erlotinib and evaluated to ...determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement.
Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS.
Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival.
Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.
We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor ...immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial.
Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals.
Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed.
Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.
Purpose: Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC),
inhibiting tumor growth in vitro and in vivo by cytostatic ...and cytotoxic mechanisms. A Phase II trial was conducted to determine the activity and toxicity of flavopiridol
in untreated patients with metastatic NSCLC.
Experimental Design: A total of 20 patients were treated with a 72-h continuous infusion of flavopiridol every 14 days at a dose of 50 mg/m 2 /day and a concentration of 0.1–0.2 mg/ml. Dose escalation to 60 mg/m 2 /day was permitted if no significant toxicity occurred. Response was initially assessed after every two infusions; patients
treated longer than 8 weeks were then assessed after every four infusions. Plasma levels of flavopiridol were measured daily
during the first two infusions to determine steady-state concentrations.
Results: This study was designed to evaluate a total of 45 patients in two stages. However, because no objective responses were seen
in the first 20 patients, the early-stopping rule was invoked, and patient accrual was halted. In four patients who received
eight infusions, progression was documented at 15, 20, 40, and 65 weeks, respectively. The most common toxicities included
grade 1 or 2 diarrhea in 11 patients, asthenia in 10 patients, and venous thromboses in 7 patients. The mean ± SD steady-state
concentration of drug during the first infusion was 200 ± 89.9 n m , sufficient for cytostatic effects in in vitro models.
Conclusions: At the current doses and schedule, flavopiridol does not have cytotoxic activity in NSCLC, although protracted periods of
disease stability were observed with an acceptable degree of toxicity.
Purpose: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly
patients with lung cancer.
Experimental Design: Previously ...untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least
70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m 2 for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week
of therapy in a subgroup of eight patients.
Results: A total of 35 patients (median age, 76 years; range, 70–85) were enrolled. The overall response rate was 23%. Median time
to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and
22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection
(8.8%). Two patients died from treatment-related toxicity. There was no significant difference ( P = 0.18) between the total body clearance of paclitaxel on the first (17.4 ± 2.9 liters/h/m 2 , mean ± SD) and sixth (15.8 ± 4.1 liters/h/m 2 ) week of therapy.
Conclusion: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m 2 is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly
patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug
clearance after repeated weekly dosing.
There are few effective treatment options for leptomeningeal metastasis (LM) in non-small-cell lung cancer (NSCLC). This study assessed the feasibility of high-dose gefitinib in patients with LM from ...NSCLC harboring EGFR mutations or prior systemic response to EGFR-TKI.
This phase I open-label trial of a novel gefitinib dosing schedule employed a 3+3 design. Eligible NSCLC patients with LM had known EGFR mutations and/or prior response to EGFR-TKI. Patients alternated 2 weeks of high-dose daily gefitinib (dose levels: 750 mg, 1000 mg, 1250 mg) with 2 weeks of maintenance therapy (500 mg daily). Primary endpoints were safety and toxicity. Secondary endpoints included overall survival (OS), neurological progression-free survival, radiological response, and cytological response in cerebrospinal fluid (CSF).
Seven patients were treated: 3 at 750 mg dose level, 4 at 1000 mg dose level. There were no DLTs at the 750 mg dose level, and one DLT (toxic epidermal necrolysis) at the 1000 mg dose level. The study was closed due to slow accrual. Median neurological PFS was 2.3 months (range 1.6-4.0 months); median OS was 3.5 months (range 1.6-5.1 months). Though there were no radiologically documented remissions of LM disease, four patients had improvement in neurological symptoms. One patient cleared their CSF of NSCLC cells, while 2 others had decrease in malignant cells in CSF.
Although the MTD was not defined due to slow accrual, this study provides important information about the tolerability and CSF penetration of high-dose gefitinib as a therapeutic option for modest palliation for NSCLC patients with LM and a known EGFR mutation.
To evaluate a nurse-led intervention to enhance medication knowledge and adherence using the Multinational Association for Supportive Care in Cancer Oral Agent Teaching Tool (MOATT).
Longitudinal, ...descriptive feasibility study.
An ambulatory thoracic oncology disease center located at the Dana-Farber Cancer Institute in Boston, MA.
30 adult patients with lung cancer who received the oral agent erlotinib.
Structured, nurse-led education sessions using the MOATT were provided, with a 72-hour follow-up telephone contact. Participants completed a Knowledge Rating Scale (KRS) and adapted Morisky Medication Adherence Scale-8 (MMAS-8) at the end of the first cycle of oral chemotherapy.
Knowledge and adherence; feasibility.
Twenty-seven participants completed the study outcome measures reporting high knowledge levels and MMAS-8 scores. Structured, nurse-led education and follow-up monitoring sessions ranged from 14-30 minutes. Several participants also initiated contact for assistance with prescription procurement and symptom management. Participants reported a median of two side effects.
The structured, nurse-led teaching, using the MOATT tool, and follow-up nurse contacts were feasible as integrated into the thoracic oncology setting. Adherence and knowledge outcomes were encouraging. Additional studies should include objective adherence measures and strategies for delivering supportive care to patients at home.
Structured teaching with patients is important to enhance proper oral anticancer medication knowledge and adherence, including follow-up monitoring of administration and side effects at 72 hours.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Purpose: To investigate the anti-tumor activity and toxicity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839 or Iressa™; AstraZeneca Pharmaceuticals, Wilmington, DE), in ...patients with advanced non-small cell lung cancer (NSCLC).
Methods: This was an open label, expanded access program (EAP) of oral gefitinib administered at 250
mg per day continuously until evidence of undue toxicity or disease progression.
Results: Two hundred consecutive patients with advanced NSCLC were enrolled in this study. The median number of prior chemotherapy regimens was 2 (range 0–6). One hundred seventy-two patients were treated with gefitinib; 23 expired from disease progression prior to treatment and 5 withdrew their consent. One hundred fifty-four patients are evaluable for toxicity; 8 (5.2%) experienced grade 3/4 toxicity; 2 patients discontinued therapy for grade 3 rash and one for grade 3 nausea. Of 172 patients evaluable for efficacy, 7 (4.1%; 95% CI; 1.7–8.2%) experienced a partial response (PR); 60 patients (34.9%) had stable disease (SD) as their best response. Median survival for all patients was 4.5 months (95% CI; 4.1–4.9 months). One-year survival was 29%. Significant independent prognostic factors associated with improved survival were female gender, good performance status (0/1), and adenocarcinoma histology.
Conclusion: Gefitinib has anti-tumor activity, in a heterogeneous population of NSCLC patients treated on the EAP study. Treatment with gefitinib in this population is associated with a longer survival in women, those with good performance status and in patients with adenocarcinomas. These findings need to be further validated in additional clinical studies.
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e19637
Background: Adherence for oral anticancer agents is a major concern for patients in the ambulatory setting. Adherence rates for oral medication regimens are associated with ...proper knowledge and monitoring for adverse side effects including symptom management. To improve patient-reported adherence we studied feasibility of a DCN educational intervention to enhance participant knowledge and adherence to erlotinib while monitoring for side effects. Methods: A prospective, pilot study with 30 NSCLC patients was conducted. The study included a DCN structured education session utilizing an adapted educational tool (MOATT) from the Multinational Association of Supportive Care in Cancer (MASCC); followed within 72 hours by a DCN phone call to assess patient learning, adherence, and adverse side effects. Primary endpoints included participant-reported Knowledge Rating Scale (KRS) scores and adherence behaviors measured by the Morisky Medication Adherence Scale (MMAS-8). Adverse side effects and feasibility data were analyzed for each DCN/patient encounter. Results: MMAS-8 adherence scores indicated medium (n=11) to high (n=14) adherence rates and high KRS scores (mean 8.9, range of 7.5-10). Mean age of patients was 67 years (range 45-84 years), majority were female (81%), with race/ethnicity as Caucasian 80%, Asian 10%, and Black 10%. Mean number of erlotinib adverse events was 2.48 per patient and 22% reported 4 or more side effects. Patients contacted DCN 60 times between start and end of protocol. Feasibility included 90% (n=27/30) completing the protocol, mean time 30 minutes to administer educational session and 14 minutes for DCN 72-hour follow-up phone call. Documentation of visits indicated nurse education and follow-up, including monitoring side effects, provided valued supportive care. Conclusions: Data supports the need for and feasibilty of a nurse-led structured protocol to enhance adherence, knowledge, and symptom management. Further study of this education/monitoring intervention for patients initiating oral anticancer agents in the ambulatory setting is recommended.
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7099
Background: Despite response to initial therapy, SCLC has high rates of relapse or distant metastasis and limited 2nd-line therapeutic options. Angiogenesis is an essential part of ...cell invasion, dissemination, and outgrowth of distant metastases and therefore is a potential therapeutic target in SCLC. Pazopanib (Votrient, GSK) is a potent, competitive inhibitor of the tyrosine kinase activity of VEGFR-1, VEGFR-2, VEGFR-3, PDGF, and c-kit. We initiated a phase II single-arm trial of pazopanib in relapsed or refractory SCLC to determine impact on disease progression. Methods: Patients were eligible if they had progressive disease following up to two lines of prior therapy. Patients were treated at the FDA-approved dose of 800 mg pazopanib once daily. The primary endpoint was progression-free rate (PFR) at 8 weeks. Secondary endpoints included median progression-free survival, overall survival, and safety. The trial followed a Simon 2-stage design to limit accrual if no therapeutic benefit was observed. Results: To date, 27 of 30 planned subjects have been enrolled since October 2010. Two did not complete cycle 1 and were considered inevaluable for response. Major toxicities (mostly grade 1/2) were those previously described including nausea, fatigue, hypertension, electrolyte abnormalities, and AST/ALT elevations (grade 3 in 4 subjects). Three subjects were removed from study due to toxicity: 1 with grade 3 nausea, 1 with grade 3 drop in the cardiac ejection fraction, and 1 with multiple grade 2 toxicities including diarrhea, fatigue, and nausea. A fourth was removed due to grade 1 hemoptysis despite clinical response. The PFR at 8 weeks of 21 subjects evaluable for response to date was 52%; 4 of these 11 subjects had chemo-refractory disease. There were no confirmed responses, but tumor regressions ranged from 2-20%. Median progression-free survival is 14.1 weeks. Conclusions: In patients with SCLC, single-agent pazopanib demonstrated a notable rate of stable disease (including among chemo-refractory patients) and a median PFS that exceeds that of historical PFS rates of < 2 months on ineffective 2nd-line therapies. These data suggest that the potential for pazopanib in SCLC treatment should be further investigated.
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