Download Poor Performance Status is not Always a Contraindication to

Poor Performance Status is not Always a
Contraindication to Systemic Therapy in
Advanced Non Small Cell Lung Cancer.
Nidhi Tandon, Vanita Noronha, Kumar Prabhash, Amit Joshi.
Tata Memorial Hospital, Dr. E. Borges Marg, Parel, Mumbai, Maharashtra.
CASE 1
A 48 year old male was referred to the outpatient
department of our centre as a case of suspected lung
carcinoma for further evaluation and management.
He presented to us in August 2010 with a history of dry
cough of 1 month duration. He had anorexia and had lost
2 kg weight in the last one month. He did not have any
complaints of dyspnoea, chest pain, backache and any
other focal neurological deficit. He was a non smoker
but used to be a social drinker. He was a diabetic and
hypertensive which was well controlled with medications.
The patient was in a good general condition with an
ECOG performance status of 1.
Key Words: NSCLC, compromised, performance status,
systemic, therapy.
The PET/ CT scan revealed a right middle lobe
mass of 4.9x5.1 cm abutting the mediastinal pleura and
pericardium with bilateral multiple lung metastases,
largest measuring 1.3x1.6 cms with multiple mediastinal
lymph nodes and sub centimeter sized axillary lymph
nodes with a small hypodense metastatic focus in
liver. The CT guided lung biopsy of the lung mass was
suggestive of adenocarcinoma. Thus, the final diagnosis
was cT2aN2M1a, Stage IV adenocarcinoma of the
lung. Keeping in mind the young age, Asian descent,
non smoker status and adenocarcinoma histology with
multiple comorbidities the patient was started on Gefitinib
as the first line therapy. EGFR mutation analysis couldn’t
be done because of logistic reasons. On follow up after 2
months the patient had improved symptomatically .The
PET /CT scan revealed a significant decrease in the
metabolism but not the size of the lung lesion and the
mediastinal lymphnodes which was suggestive of a stable
disease by anatomic criteria and a partial response by the
metabolic criteria. Hence the patient was continued on
the same therapy.
However the patient came 1 month later in December
2010 with giddiness,ataxia and marked weakness. His
performance status was 3. The patient had an MRI of
the brain which revealed left cerebellar metastasis with
perilesional edema; however the CT scan of the thorax
and abdomen still had stable disease. The patient was
Corresponding Author: Dr. Kumar Prabhash, Tata memorial hospital, Dr. E. borges marg, Parel, Mumbai, Maharashtra.
E-mail: [email protected]
103
Nidhi Tandon
given symptomatic treatment in form of steroids and
whole brain irradiation. In view of overall progression of
the disease he was started on second line chemotherapy
with Pemetrexed and Carboplatin. The patient had about
50% improvement in weakness and was able to move
around by himself after the first cycle only. He developed
grade 1 alopecia and grade 2 mucositis and skin rash. With
subsequent cycles, his performance status progressively
improved to ECOG 1 and the restaging PET/CT scan
revealed a 58% reduction in the measurable lesion
suggestive of a partial response to therapy. The patient
remained asymptomatic and the imaging continued to
show a similar response hence the patient was started
on maintenance Pemetrexed after completion of the 6
cycles in May 2011.
Again the patient developed increasing cough and
breathlessness at rest after 2 months because of which
the performance status again deteriorated to 3. The PET/
CT scan was suggestive of increase in number, size and
extent of bilateral lung nodules although the lung mass
remained the same and the mediastinal lymphnodes had
completely regressed, overall suggestive of progressive
disease. The patient was started on weekly Paclitaxel at
80 mg/m2 and 3 weekly Carboplatin AUC 5, to which
he responded dramatically and started performing all his
day to day activities by himself. At present the patient is
doing well and is due for his third cycle of chemotherapy.
CASE 2
A 46 year old non smoker male with no comorbidities
presented to us with breathlessness on exertion which
gradually progressed to breathlessness at rest in duration
of 3 months. This was associated with dry cough and
low grade fever but no weight loss. On examination
the patient had extensive crepitations in bilateral lung
GRADE
fields. The patient was in a poor general condition with
a performance status of 3 and required non invasive
ventilatory support outside. The CT scan revealed diffuse
nodular involvement of both lungs with the largest
nodule being of the size 1.9x1.8 cm in the anterior basal
segment of the right lower lobe giving an appearance of
bronchioalveolar carcinoma. The CT guided biopsy of the
right lung nodule was suggestive of adenocarcinoma and
the sputum cytology also showed scanty non small cells.
Due to poor performance status the patient couldn’t be
given any intravenous chemotherapy or targeted therapy.
However in view of the young age, non smoker status,
asian descent, histological appearance of adenocarcinoma
and radiological appearance of bronchioalveolar
carcinoma, the patient was started on Gefitinib. EGFR
analysis was however not done. The patient showed a
dramatic improvement with improvement of performance
status to 1 within the next 1 month. The imaging done
after 3 months revealed no significant change in the
size and number of the lung nodules suggesting a stable
disease. Hence the patient was continued on gefitinib . In
the response assessment after 6 months the patient was
found to be asymptomatic with the CT scan suggesting
a decrease in size of the target measurable lesions from
1.5 to 1.2 cms depicting a stable disease. The patient is
doing well at present and is being continued on gefitinib.
DISCUSSION
Performance status (PS) is a strong independent
prognostic factor for survival of patients with advanced
non small cell lung cancer (NSCLC).1, 2
Two scales are commonly used to grade PS for lung
cancer: the Eastern Cooperative Oncology Group
(ECOG) scale (0–5) and the Karnofsky scale (100–0).
ECOG PERFORMANCE STATUS (3)
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or
sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about
more than 50% of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5
Dead
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Poor Performance Status not Always a Contraindication to .....
KARNOFSKY PERFORMANCE STATUS SCALE
DEFINITIONS RATING (%) CRITERIA (4)
Able to carry on normal
No special care needed
100 Normal no complaints; no evidence of disease.
90 Able to carry on normal activity; Minor signs or symptoms of
disease.
80 Normal activity with efforts; some signs or symptoms of disease.
Unable to work; able to live at
home and care for most
personal needs; varying amount of
assistance needed.
70
60
Unable to care for self; Requires
equivalent of institutional or
hospital care;
diseases may be progressing
rapidly.
40
30
50
20
10
0
Cares for self; unable to carry on normal activity or to do active work.
Requires occasional assistance, but is able to care for most of his
personal needs.
Requires considerable assistance and frequent medical care.
Disabled; requires special care and assistance.
Severely disabled; hospital admission is indicated although death not
imminent.
Very sick; hospital admission necessary; Active supportive treatment
necessary.
Moribund; fatal processes progressing rapidly.
Dead
In 2002, Schiller J, et al5 randomized 1207 patients with advanced non–small-cell lung cancer to a reference
regimen of cisplatin and paclitaxel or to one of three
had ECOG PS of 2. These patients with PS 2 were
experimental regimens: cisplatin and gemcitabine,
more likely to present with weight loss, leucocytosis
cisplatin and docetaxel, or carboplatin and paclitaxel.
and anaemia. The response rates to chemotherapy in
She concluded that none of four chemotherapy regimens
patients with good PS versus poor PS patients were
offered a significant advantage over the others. She also
38% and 28% respectively (p=0.06). Overall, 25% of
found that patients with a performance status of 2 had
the patients had an improvement in PS from 2 prior to
a significantly lower rate of survival than did those with
3-drug-combination chemotherapy, to PS 0 to 1 after
a performance status of 0 or 1 (Median survival among
chemotherapy. Performance status significantly improved
patients with a PS of 0 was 10.8 months, as compared with
during chemotherapy not only in the 38% of patients who
7.1 months for PS of 1 and 3.9 months for PS of 2 with
achieved a response to chemotherapy, but also in 20% of
P<0.001). The accrual of patients with an ECOG PS of 2
patients who achieved stable disease and in 14% patients
was discontinued due to a perceived rate of unacceptable
who had disease progression on chemotherapy. Response
toxicity. Sweeney et al6 evaluated 64 patients of ECOG
to chemotherapy predicted for a faster and deeper
PS 2 or more randomized to one of the above mentioned
improvement in PS. PS was found to be a significant
arms and found that patients with advanced NSCLC
predictor of survival: PS 0-1 patients had a median OS
of 10.2 months, while PS 2 patients had a median OS
and a PS of 2 experienced a large number of adverse
of 5.5 months, p<0.001. Regardless of the baseline PS,
reactions and overall poor survival. A comparison with
patients who responded to chemotherapy had a similar
patients with a PS of 0-1 suggests that these events and
survival. A major concern of administering combination
the shorter survival were related to disease process rather
chemotherapy to poor PS patients is the increased risk of
than treatment.
toxicity. There was no difference in hematological toxicity
between PS 0-1 and PS 2 patients; there was more grade
A similar finding was concluded by European Lung
III alopecia in the PS 0-1 patients, while there was more
Cancer Working Party who did a retrospective analysis
diarrhea and cardiac toxicity in PS 2 patients. There were
of a prospective randomised trial performed in advanced
more toxic deaths in the PS 2 patients: 9.2% as compared
NSCLC where 485 patients received three courses
to 2.1% in PS 0-1 patients (p=0.002).7
of gemcitabine +ifosphamide +cisplatin induction
chemotherapy.20% of these patients, i.e. 98 patients
Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 12, No. 2, April 2013
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Nidhi Tandon
This was implemented in the 2003 American Society
of Clinical Oncology (ASCO) guidelines which suggested
that chemotherapy should be offered only to patients
with good performance status, i.e ECOG PS 0 to 2.8 This
recommendation is echoed in the current 2011 guidelines
as well.9 Thus, for patients with poor PS (ECOG 3 or 4),
best supportive care is recommended.
As regards the oral tyrosine kinase inhibitors also, the
INSTEP trial10 showed no survival benefit for gefitinib
in patients with PS 2 or 3 compared with placebo. The
TOPICAL trial11 randomized chemo-naïve NSCLC
patients stage IIIB/IV unfit for platinum chemotherapy;
which included patients with ECOG PS 2 OR 3 to Erlotinib
(150 mg/d) plus BSC or placebo plus BSC. They found
that Erlotinib improved outcomes for female but not for
male patients, regardless of histology and mutation status.
Also, the BR 2112 study was a double-blind phase III trial
that randomly assigned 731 patients with NSCLC who
had progressed after prior chemotherapy to erlotinib 150
mg daily or placebo, with survival as the primary end point
and Quality of life (as assessed by European Organisation
for Research and Treatment of Cancer QLQ-C30 and the
lung cancer module QLQ-LC13) as the secondary end
point. They found that those on erlotinib had significantly
longer survival (hazard ratio, 0.70; P < .0001), longer
median time to deterioration for symptoms of cough,
dyspnea and pain and a significant improvement in the
physical function (31% erlotinib versus 19% placebo, P<
.01), and global QOL (35% v 26%, P< .0001).
We found that both our patients with poor performance
status showed a response to systemic therapy. In the first
patient the poor performance status was related to the
brain metastasis at the first relapse and progressive lung
disease in the second relapse. As regards to the second
patient he was in a poor general condition due to the
disease involving bilateral lung fields. However, both these
patients had a dramatic improvement in the performance
status from 3 to 1 after starting systemic therapy. Also,
what needs to be noted that both these patients did not
have any major hematological and non hematological
toxicities related to the treatment. This suggests that not
all patients with poor performance status should be denied
systemic treatment. A select subset of PS 3 patients may
benefit from therapy, either chemotherapy (single agent or
combination) or oral TKI, with amelioration of symptoms,
improvement in their quality of life and possibly prolonged
survival. It may be worthwhile to consider performing a
prospective clinical trial on this subset of PS 3 patients
to best determine who are the patients who benefit from
systemic therapy.
Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 12, No. 2, April 2013
CONCLUSION
In conclusion, these two cases show that chemotherapy
is beneficial in patients with poor performance status
(ECOG PS 3), as shown by a significant improvement
in performance status. Not all patients of advanced non
small cell lung cancer should be denied treatment because
of poor performance status.
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