BOOK REVIEWS
STAGE 4 NON-SMALL CELL LUNG CANCER
(Excerpted from Lung Cancer
and Mesothelioma)
keywords, stage 4 treatment, clinical trials, stage 4
treatment, advanced
lung cancer, treatment, stage 4 treatment alternatives.
20.1 SUMMARY OF STAGE 4 TREATMENT
20.11 Overview
Stage 4 means the tumor has metastasized to another organ. Surgery is
generally not an
option with scientists reasoning that removal of a lung tumor while leaving
visible or microscopic metastases will not effect a cure. Current science
reasons the benefit is questionable and the procedure carries significant risk.
Clinical trials to confirm this have been limited.
Chemotherapy is the standard treatment for these disseminated tumors.
Response rates for particular drugs are in the 20-25%, with rates a alittle
higher or multi-drug regimens. There are periodic reports of patients with
3 and 5 year survivals after chemotherapy, and clinical trials occasionally
report complete responses. Many patients do not respond to chemotherapy
and other develop resistance after response. Thus second line treatment
after initial response is part of lung cancer treatment. chemotherapy may
also improve quality of life by reducing disease-related consequences, and side
effects like nausea are less than in the past.
Radiation in the lung area is designed to reduce pain or discomfort.
Cancer is started by abnormal growth factors. One such growth factor is the epidermal growth factor receptor (EGFR). Patients who are EGFR positive have response rates of an astronomical 60% using Tarceva and EGFR inhibitor, almost triple that of conventional chemotherapy. EGFR patients are primarily non-smokers with adenocarcinoma, but that is not exclusive. Some light and even an occasional heavy smoker is EGFR positive and some non-smokers are not EGFR positive. Testing the patient for the mutation and contouring treatment based upon that makes sense.
Only about 10% of patients are EGFR positive. However, the lessons of testing are expanding. Rather than simply generalize about treatment, why not conduct specialized testing and prescribe drugs specifically designed to address the offending growth factor. There are difficulties. Non-smokers lung cancer non-smokers lung cancer is probably simpler with one or perhaps few growth factors, while smoker's cancer appears to involve multiple growth factors. Nonetheless, to test for particular growth factors and treat based upon the test makes logical sense with clinical trials needed to confirm the theory's efficacy with particular drugs. Cox-2 is being evaluated with a recent study showing Celebrex a Cox-2 inhibitor showing some promise with Cox-2 patients.
Keywords, cancer lung, stage 4 treatment cancer lung,
stage 4 survival statistics, fatigue,
symptoms, Stage 4 lung cancer, lung non small.
cancer lung stage, cancer lung symptom,
lung treatment, alternative treatment, small cell lung cancer, fatigue,
symptoms, Stage 4 lung cancer, lung non small.
cancer lung stage, asbestos cancer lung, lung cancer cause cancer, survival
rate, information, cancer lung type, statistics, lung cancer stage 4,
20.12 The Broad Scope of the Stage 4 Category
Stage 4 has many variations since the number of organs, the extent of
metastasis, and other factors impact the period of survival and chances for
cure. Stage 4 would include an elderly patient with extensive COPD (chronic
obstructive pulmonary disorder) and extensive metastasises as well as a
middle-aged patient with a single metastasis and otherwise good health. Given
the variation in disease type, patient status, and extent of metastasis, one
must be careful with general assessments of stage 4 patients.
New research is showing that patients respond differently based upon their
subtype. Adenocarcinoma and BAC patients who did not smoke or smoked little had
over 65% response rates to Iressa and Tarceva in several recent studies. (A
separate chapter is devoted to epidermal growth factor inhibitors so I will only
summarize findings here.)
20.13 Varying Survival Statistics for Stage 4
Survival reports differ. Some are favorable: “The 5-year cumulative survival
rate was 88.0% for patients in stage IA, 53.9% in stage IB, 33.5% in stage II,
14.7% in stage IIIA, 5.5% in stage IIIB and 7.0% in stage IV.” Wu (1). “The
5-year survival rates for these patients were as follows: stage I, 68.5%; stage
II, 46.9%; stage IIIA, 26.1%; stage IIIB, 9.0%; and stage IV, 11.2%.” Naruke
(2). Others are dim, reporting survival rates of 20-30 weeks in clinical trials,
even those receiving chemotherapy.
It may well be the status of the patient, since we know that the overall health
or performance status, as well as the number of lymph nodes involved and other
factors influence survival. A 45 year patient with a small area of metastasis in
otherwise good health should do better than an older patient with COPD and
multiple metastases. Those looking for hope can legitimately find it, not in
bizarre reports from other countries, but legitimate clinical trials. Those
looking for stark reality may find that the prospects of overall cure are
limited.
20.14 Mental Attitude
Some would suggest attitude can play a role and that the willingness to fight
and undergo treatment can extend life. The author of The Cancer Patients
Handbook wrote the book while 3 years post-diagnosis for stage 4 NSCLC.
A patient in a support group wrote:
“I was diagnosed 7/99 with stage 4 NSCLC and chose to have chemo (taxol and
carboplatin). Over three years later I am in remission and still enjoying life.
I grant you that it is not life as I knew it before, but it is still quite
enjoyable. So please, everyone who has lung cancer, don't think there isn't any
use to fight it. I am living proof that for some, the outcome is NOT always the
same and there is a possibility of living much longer than the statistics say.”
Acor.org support group.
20.2 CHEMOTHERAPY
20.21 Chemotherapy Is Standard
Chemotherapy is the primary form of treatment for stage 4 and serves to extend
life and frequently reduce cancer-related symptomology. While there is near
agreement that chemotherapy is beneficial, the exact form of chemotherapy which
should be used remains unclear, though the combination of Taxol and Carboplatin
is generally given today (March, 2002). Carboplatin, vinorelbine, taxol,
gemcitabine and other forms of chemotherapy have displayed benefits, but the
optimal mix of drugs remains unclear since clinical trials have reached varying
results. There is detailed information on the Internet about clinical trials
with different chemotherapy combinations. One must be careful not to place undue
emphasis on the result of a single trial, for it is only consistent results
which can create a standard of care. There is an emerging consensus that
multi-modal chemotherapy is preferable to single agent, though scientists may
struggle to minimize side effects.
The National Cancer Institute states,
“Cisplatin-containing and carboplatin-containing combination chemotherapy
regimens produce objective response rates (including a few complete responses)
that are higher than those achieved with single-agent chemotherapy. Although
toxic effects may vary, outcome is similar with most cisplatin-containing
regimens... Two small phase II studies reported that paclitaxel (Taxol) has
single-agent activity in stage IV patients, with response rates in the range of
21%- 24%. Reports of paclitaxel combinations have shown relatively high response
rates, significant 1 year survival, and palliation of lung cancer symptoms. With
the paclitaxel plus carboplatin regimen, response rates have been in the range
of 27%-53% with 1-year survival rates of 32%-54%. The combination of cisplatin
and paclitaxel was shown to have a higher response rate than the combination of
cisplatin and etopiside. [8]. Additional clinical studies should better define
the role of these newer combination chemotherapy regimens in the treatment of
advanced non-small cell lung cancer. Meta-analyses have shown that chemotherapy
produces modest benefits in short-term survival compared to supportive care
alone in patients with inoperable stages IIIb and IV disease.” www.nci.net.
20.22 Carboplatin Compared with Cisplatin
Carboplatin and Cisplatin are both platinum-based chemotherapy drugs.
Carboplatin has fewer side effects and essentially the same impact, so it is
used more often.
20.23 Physician’s Attitudes and Chemotherapy
Many physicians will be familiar with recent favorable developments in treatment
for advanced lung cancer. Some may be negative and one writer explains why:
“Early trials in NSCLC (non small cell lung cancer) did not show the
improvements in survival with SCLC. Indeed, the earliest regimens, based upon
alkylating agents rather than cisplatin, appeared detrimental. Physicians
attitudes to chemotherapy for NSCLC were therefore profoundly negative, and have
tended to remain so. Subsequent combination chemotherapies have yielded some
improvements in survival, as well as symptom relief as described above.
Unfortunately, attitudes have not changed despite the now-abundant evidence that
chemotherapy is superior to supportive care.” Pass (1), at 998.
20.24 The Creation of Multi-Drug Resistance
Chemotherapy has served to extend life and reduce symptoms, but it has
unfortunately not served as a cure for most stage 4 lung cancer patients. Even
those patients who respond initially to chemotherapy frequently develop
multi-drug resistance (MDR). For this reason, attention has focused on gene and
other therapies for stage 4 patients.
20.25 Chemotherapy as Improving Quality of Life
There is significant evidence that chemotherapy improves quality of life.
“There is evidence that most patients either improve or preserve their
performance status during treatment. In one report on the MIC (mitomycin C,
ifosfamide, cisplatin) regimen, only 9% of patients experienced deterioration in
quality of life on treatment, and 30% improved. It is also well documented that
improvements in symptoms are not confined to patients with an objective
response.” Pass (1), at 909.
Devita’s well-known cancer treatise states:
“Disease-related symptoms will improve after chemotherapy, sometimes even in the
absence of a measurable tumor response. QOL scores improved with chemotherapy,
whereas they declined over the first 6 weeks with best supportive
care....Improved survival and QOL were also demonstrated with single agent
chemotherapy in a population of patients exceeding the age of 70 years.” (Devita
3) at 969.
See Bianco (4) (improvement in quality of life of elderly patients seen after
Gemcitabine chemotherapy). However, each individual will need to make
determinations of the type of treatment based not only upon statistics but an
individualized assessment of the patient’s condition.
20.251 Substituting Other Drugs for Cisplatin
Cisplatin was one of the most widely-used chemotherapy for a number of years,
and its efficacy has been shown in clinical trials. However, it has been
associated with nausea and vomiting. Other drugs are being used to replace
Cisplatin with similar effectiveness but without these side effects. Taxol,
Carboplatin, and Gemcitabine are three widely used substitutes.
20.26 Multi-Modal Chemotherapy
Combining drugs improve response. Taxol and Carboplatin is the most widely used
combination, though any number of combinations have been tried including
Cisplatin and Gemcitabine, Carboplatin and Gemcitabine, Cisplatin and
Vinorelbine. Whether three drug combinations further improve response is
unclear.
20.3 RADIATION
20.31 Local Control and Palliation
Radiation is used to diminish tumor size, reduce pain, and improve breathing
ability. Radiation will generally not eradicate the entire tumor, putting aside
the areas of metastasis.
20.4 GENE THERAPY
20.41 Egfr Treatment
Tarceva and Iressa have shown substantial effectiveness for a narrow group of EGFR positive patients. Since Tarceva and Iressa are tyrosine kinase, EGFR inhibitors, it is not surprising they are effective with EGFR patients. The Harvard Gene Laboratory contacts a genetic test which generally finds that non-smokers and very light former smokers who have quit are EGFR positive.
Tarceva and Iressa's benefits outside this target group is unclear.
Because the drugs impact only a limited number of cells, their side effects are
limited and the drugs continue to be evaluated.
20.5 ANTI-ANGIOGENIC THERAPY
The primary danger of stage 4 cancer is the propensity to metastasize, and
attention is paid to anti-angiogenic drugs which attempt to inhibit
angiogenesis, the process by which tumors form new blood vessels and pathways
through which the tumor can metastasize.
20.51 Avastin
Avastin has received FDA approval for certain non-small cell patients, and is
designed to inhibit VEGF. "Preliminary results from a large, randomized clinical trial for patients
with previously untreated advanced non-squamous, non-small cell lung cancer show
that those patients who received bevacizumab (Avastin™) in combination with
standard chemotherapy lived longer than patients who received the same
chemotherapy without bevacizumab."
A total of 878 patients with advanced non-squamous,
non-small cell lung cancer (NSCLC) who had not previously received systemic
chemotherapy were enrolled in this study between July 2001 and April 2004.
Patients were randomized to one of the two treatment arms. One patient group
received standard treatment -- six cycles of paclitaxel and carboplatin. The
second group received the same six-cycle chemotherapy regimen with the addition
of bevacizumab, followed by bevacizumab alone until disease progression.
See the manufacturer's website. www.anti-vegf.com
20.52 How Avastin Works
The vascular endothelial growth factor (VEGF) is associated with metastasis. Angiogeneis is the process by which new blood vessels and related sources of blood supply are developed in cancer patients. The process occurs in healthy people; we need to develop sources of blood supply for growth, repair of damaged tissue. In cancer patients, angiogenesis facilitates metastasis, spread of cancerous cells to other organs. VEGF is a growth factor which prompts this process. Inhibition of VEGF and with it angiogenesis holds forth the prospect of limiting metastasis and improving survival. More technically:
VEGF is essential for establishing a functional vascular system during embryogenesis and early postnatal development, but has limited physiological activities in adults. Studies in mice have shown that: targeted disruption of one of the two copies of the VEGF gene results in embryo death (Figure 1) VEGF inactivation during early postnatal development is also lethal VEGF and angiogenesis are also required for endochondral bone formation, the mechanism by which bone grows longitudinally in vertebrate development, and therefore VEGF inhibition in young animals causes growth restriction. See Sandler (7) (8)
20.53 Avastin Side Effects
Blood related side effects were found:
"The most significant adverse event observed in this
study was life-threatening or fatal bleeding, primarily from the lungs. This
occurred infrequently, but was more common in the patient group that received
bevacizumab in combination with chemotherapy than in the patient group that
received only chemotherapy. A fuller description of side effects observed in
this trial were presented at the ASCO press briefing as well. These included
information that both treatment regimens were well-tolerated, with the most
common side-effects being low white blood cell counts (24 percent on bevacizumab
vs. 16 percent on standard chemotherapy), blood clots (3.8 percent vs. 3.0
percent)and bleeding (4.1 percent vs. 1.0 percent). "
Certainly the side effects would indicate awareness and monitoring by
physician and patient. Whether certain subgroups should not take the
combination remains to be seen.
20.6 SITES OF METASTASIS FOR LUNG CANCER
20.61 The Variability of Metastatic Behavior in Lung Cancer
Exactly where and when a tumor will metastasize is difficult to determine:
“It has been known that the biological behavior of NSCLC is heterogeneous; for
example, distant metastasises occur early in most patients, but late in others,
and there are also significant differences in responsiveness to irradiation or
chemotherapy, even in patients with the same histological type.” Fu, (5).
The frequent sites for distant metastasises were the bone, brain, liver and
adrenal glands. Hanigiri, (6).
20.62 Brain
Approximately 10% of non-small cell patients will have some type of brain
metastasis at time of presentation and by time of death, some 30% of patients
will display some evidence of cranial metastasis. Pass (6) at 1011, (Quantin,
(7), Rodriqus(8). Family members need to be alert to significant changes in
personality or functioning. Single metastasises account for 30-50% of
metastases. Pass (6) at 1011.
Radiation is the primary treatment though surgery may also be utilized. Some
have advocated stereotactic radiosurgery, the use of computerized techniques to
identify targets and focus large single doses of radiation on specific areas,
while attempting to minimize exposure to adjoining tissues. Chemotherapy is used
to generally combat metastatic cancer, while radiation and surgery are directed
to specific areas.
20.63 Bone
A study found that 13% of non-small cell patients had bone metastasis. Hanigiri,
(7). Bone scanning is a sensitive examination to detect bone metastases. A
standard x-ray is also possible but,
“Fifty per cent of bone material content must be lost before changes are
apparent on plain radiographs.... [Thus] plain radiograph is an insensitive
method of investigating localized bone pain. Radiopharmaceutical bone scans are,
in contrast, highly sensitive though non-specific. Bone scanning is thus only
indicated in those patients who have bone pain, elevated alkaline phosphatase
levels, or recent exacerbation of bone pain... MRI may be useful to assess
localized areas of persistent bone pain which appear normal on bone scan and
plain radiographs.” Carney (10) at 65-66.
20.7 PSYCHOLOGICAL ISSUES AND THE PHYSICIAN
Results vary for stage 4 patients. While most will pass away within a year, some
will survive longer. Again, the large number of people with different areas of
metastases, subtypes, age, and performance status makes prediction difficult.
Many patients and their families will want to be fighters, searching for the
best treatment, and maintaining a positive approach in the face of adversity.
Not every physician will have this approach. Some doctors worry that if they
predict or suggest success, they will be blamed for failure, the patient
reasoning that the doctor’s lack of skill or knowledge was the cause. Thus, some
doctors will present a pessimistic approach. Other physicians may present a
positive and optimistic, and sometimes be blamed for subjecting a patient to
difficult chemotherapy when the chance of a cure was small.
It is therefore important to carefully select a physician and, if need be, make
a change. Family members may have to push some doctors to be aggressive. On an
aggregate basis extensive chemotherapy may not be cost-effective for a 75 year
old man when measured against the time period that life is extended. However, no
family member would want such cost considerations to infringe upon decisions for
his or her family member.
So beware of the negativity which may be present in some circumstances.
Countering it may not be accepting undocumented claims of cure, it is
aggressively seeking prompt diagnosis and the best treatments. Where a
particular drug does not appear to be working the aggressive patient will ask to
have its impact evaluated and be willing to test another drug regimen.
20.71 Performance Status as the Best Indicator of Survival
While stage and extent of metastasis are important, performance status continues
to be the critical factor in determining the patient’s status. Performance
status is a medical term which evaluates a patient’s mobility and status. An
ambulatory patient conducting his usual activities has a high performance
status, a bed-ridden fatigued patient would have a low performance status. The
fact that a patient is bed-ridden, severely fatigued, or immobile is likely to
be the most reliable indicator of poor prognosis:
“Three studies that have included large numbers of patients with cancer at all
stages found that functional or performance status was the accurate predictor of
survival. Decline in activities of daily living including bathing, continence,
dressing and transfer, were very strongly associated with decreased survival.” (Devita
6).
REFERENCES
1. Wu, Post-operative staging and survival based on the revised TNM staging
system for non-small cell lung cancer, Zhonghua Zhong Liu Za Zhi 1999
Sep;21(5):363-5.
2. Naruke, Implications of staging in lung cancer, Chest 1997 Oct;112(4 Suppl):242S-248S.
3. Devita, Principles and practice of Oncolology (6th Ed. 2001).
4. Bianco, Gemcitabine as single agent chemotherapy in elderly patients with
stages III-IV non-small cell lung cancer (NSCLC): a phase II study. Anticancer
Res 2002 Sep-Oct;22(5):3053-6.
5. Guarino, A dose-escalation study of weekly topotecan, cisplatin, and
gemcitabine front-line therapy in patients with inoperable non-small cell lung
cancer, Oncologist 2002;7(6):509-15.
6. Devita, Cancer Principles and Practice of Oncology 3078 (Lippincott 2001).
7. Sandler, Randomized phase II/III
Trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC #
704865) in patients with advanced non-squamous non-small cell lung cancer
(NSCLC): An Eastern Cooperative Oncology Group (ECOG) Trial – E4599. J Clin
Oncol 2005; 23 (June 1 Suppl.): 2s (Abstract LBA4)
8. Lung Cancer Highlights from ASCO 2005, The Oncologist, Vol. 11,
No. 1, 39-50, January 2006; doi:10.1634/theoncologist.11-1-39
keywords, stage 4 treatment, clinical trials, advanced lung
cancer, treatment,
OTHER BOOK EXCERPTS
Lung cancer and Mesothelioma ( The book Lung Cancer and Mesothelioma in Word format, formatting
varies from published version)
What is
cancer basic concepts of cancer development, growth factors, oncogenes.
cancer terminology partial and complete response, methods of evaluating
drugs, causation,
how lung cancer develops concepts of genetic damage and alteration,
screening and identification of tumors
diagnostic tools and their accuracy Chest x-ray, Ct Scan, Pet Scan,
Types of lung cancer Small cell and non-small cell distinctions
Iressa Analysis of Iressa and epidermal growth factor inhibitors.
Cancer weight loss and fatigue Cachexia, lung cancer pain and fatigue.
Anti-angiogenic drug overview discussion of drugs to limit cancer
metastasis.
Small cell lung cancer staging and treatment standard and other staging
methods,
surgical options, chemotherapy and drug resistance.
health insurance issues
Overview of Mesothelioma
surgery and radiation for mesothelioma
chemotherapy for mesothelioma
Standard of care for diagnosis of lung cancer
Resource sources
Lung cancer family history and diet
Other
books on Lung Cancer
BOOK REVIEWS
Quality Books
"This book provides an invaluable resource for anyone who has or who is caring
others with Mesothelioma or other Lung cancers. It provides a wealth of relevant
and useful information on various types of lung cancers, medical trials,
treatments and medications. This well researched and comprehensive book is quite
unique on the subject. This book also contains a detailed discussion on the
emotional burden of Lung Cancer upon the patient and their families and ways to
manage it."
Lorraine Kember. Author of "Lean on Me -
Cancer through a Carer's Eyes", "The very
mention of the word Cancer, strikes fear into all of us.... From personal
experience I know that knowledge is the key to providing a better "quality of
life" for the cancer patient. Better understanding of the stages of the disease
and of methods and medications available to treat the pain and symptoms caused
by it, allow for the patient and those who care for them, to make informed
decisions regarding their care. In this way, they are able to regain some
control over their lives. Rarely does one find all the information they need in
one book, however I believe Howard's well researched and comprehensive book
"Lung Cancer & Mesothelioma", is quite unique. It provides a wealth of relevant
and useful information including; how various types of cancer are formed,
medical trials, available treatments and medications, insight and discussion
regarding the emotional burden of cancer upon the patient and their families and
ways by which to manage grief. I believe this book will provide an invaluable
resource for anyone who has or who is caring for someone with cancer.
Profile
Howard Gutman is a New Jersey attorney based in Parsippany, New Jersey who has handled numerous legal claims involving pulmonary tumors. A member of the board of directors of a leading cancer support group and a caregiver, he is the author of the new book Lung Cancer and Mesothelioma. In his legal capacity, he has appeared on Good Day New York, spoken at the National Press Club and been interviewed by NBC Nightly News.
Keywords, cancer lung, stage 4 treatment cancer lung,
stage4 3 year survival statistics, atigue,
symptoms, Stage 4 lung cancer, lung non small.
cancer lung stage, cancer lung symptom,
lung treatment, alternative treatment, small cell lung cancer, fatigue,
symptoms, Stage 4 lung cancer, lung non small.
cancer lung stage, asbestos cancer lung, lung cancer cause cancer, survival
rate, information, cancer lung type, statistics, lung cancer stage 4,
Disclaimer This page is not intended to provide medical advice or treatment. Some of the information on this site may not be relevant to your condition, and all advice should be obtained from a physician. The materials herein are intended to provide general information and no representation or made as to its completeness or accuracy.