PREVALENCE OF CIGARETTE SMOKING AMONG TEEANAGER IN MIDSAYAP AREA

AN UNDERGRADUATE THESIS OF GRADE 12 STUDENTS TO MRS.SOLEDOM

 CHAPTER 1

BACKGROUND OF THE STUDY

Introduction

Smoking is a practice in which a substance is burned and the resulting smoke breathed in
to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried
leaves of the tobacco plant, which have been rolled into a small square of rice paper to create a
small, round cylinder called a "cigarette". Smoking is primarily practiced as a route of
administration for recreational drug use because the combustion of the dried plant leaves
vaporizes and delivers active substances into the lungs where they are rapidly absorbed into the
bloodstream and reach bodily tissue. In the case of cigarette smoking these substances are
contained in a mixture of aerosol particles and gasses and include the pharmacologically active
alkaloid nicotine. Smoking generally has negative health effects, because smoke inhalation
inherently poses challenges to various physiologic processes such as respiration.

The epidermal growth factor receptor (EGFR) and its family members, ligands, and
downstream effectors have emerged as leading targets in treating non–small cell lung cancer
(NSCLC). Activation of the EGFR by ligand binding or mutation stimulates cellular growth,
proliferation, invasion, and metastasis and inhibits apoptosis (Mendelsohn, 2000).

Gefitinib is a synthetic anilinoquinazoline that inhibits the EGFR tyrosine kinase in vitro
with an concentration that inhibits 50% of 0.027 to 0.33 mol/L, which is 100 times lower than
the concentration required to block the kinases of HER-2, KDR, MEK-1, and MEK-2 (Wakeling,
Guy & Woodburn et al, 2002). Three phase I trials have been reported (Ranson, Hammond,
Ferry, Baselga, Rischin, Ranson, Herbst, Maddox, Rothenberg et al, 2002), -and in two of these
major objective responses were observed in patients with NSCLC refractory to multiple prior
chemotherapy regimens. Overall, 10% of NSCLC patients treated on these trials (10 of 100
patients) experienced partial responses that were often accompanied by prompt symptomatic
improvement.
 The phase I data prompted two phase II monotherapy trials designed to determine the
objective response rate and measure the frequency and magnitude of symptomatic benefit in
patients with NSCLC previously treated with chemotherapy [6,7]. In these trials, radiographic
regressions were observed in 14% of patients (61 of 426 patients; 95% CI, 11% to 18%) and
symptomatic improvement in 39% of patients (165 of 426 patients; 95% CI, 34% to 43%). These
results confirmed those suggested by the phase I trials of rapid and durable responses with
clinically meaningful benefit for some patients. Although response rates were modest, these
results compare favorably with those of cytotoxic agents commonly used in this setting (Fossella,
DeVore, Kerr, Shepherd, Dancey & Ramlau et al, 2000).

As EGFR is present in essentially all NSCLC tumors and drug concentrations sufficient
to inhibit EGFR tyrosine kinase activation are achieved in most patients, the phase II
investigators sought to identify pretreatment clinical characteristics predictive of radiographic
regressions. In terms of radiographic response, which in both phase II trials was a surrogate for
symptomatic benefit, the most striking differences reported were noted by sex and histologic
subtype of NSCLC. Responses were seen in 25% (95% CI, 18% to 32%) of women (39 of 154
patients) as compared with 8% (95% CI, 5% to 11%) of men (22 of 270 patients) and in 19%
(95% CI, 15% to 24%) of patients with adenocarcinoma (53 of 274 patients) as compared with
eight of 150 patients or 5% (95% CI, 2% to 9%) in other NSCLC histologist. Patients enrolled in
Japan had higher radiographic response rates in the Iressa Dose Evaluation in Advanced Lung
Cancer (IDEAL) 1 trial (Fukuoka, Yano & Giaccone et al, 2003).

Thus to see if we could identify other pretreatment variables that predicted sensitivity to
this agent, we undertook this retrospective review of Memorial Sloan-Kettering Cancer Center
patients. We paid particular attention to cell type and smoking history, variables not addressed in
the multicenter trials.
Statement of the problem