Download Retreatment of Patients Surviving Cancer-Free 2

Retreatment of Patients Surviving
Cancer-Free 2 or More Years After Initial
Treatment of Small Cell Lung Cancer*
John P. Chute, MD; Michael J. Kelley, MD; David Venzon, PhD;
John Williams, MD; Allen Roberts, MD, FCCP; and
Bruce E. Johnson, MD
Study objective: To assess the outcome after retreatment of patients with small cell lung cancer
(SCLC) who redevelop small cell cancer (SCC) 2 or more years after initial therapy.
Design: Retrospective analysis.
Setting: Single government institution: the National Cancer Institute.
Patients: Twenty patients who redeveloped SCC among 65 patients who survived 2 or more years
after starting treatment for their initial cancer.
Measurements: The response rate of patients after retreatment, the survival duration from the time
of redevelopment of SCC, and the toxicities of retreatment.
Results: Twenty patients redeveloped SCC: 18 with a relapse and 2 with a second primary cancer.
Sixteen received treatment after they redeveloped SCLC while four did not. Eleven patients were
retreated with chemotherapy alone, two patients received chemotherapy plus chest radiotherapy,
one patient received radiotherapy alone, one patient underwent lobectomy, and one patient was
treated with a monoclonal antibody followed by chemotherapy. Nine of 16 patients (56%) treated
after they redeveloped SCLC had an objective response (3 complete and 6 partial). The median
survival of all 20 patients after they redeveloped SCC was 3.9 months (range, 0 to 46 months). The
median survival of the patients who were retreated was 6.5 months (range, 1 to 46 months).
Conclusions: Patients who suffer relapses with SCLC 2 or more years from diagnosis are candidates
(CHEST 1996; 110:165-71)
for retreatment.
Key words: carcinoma; lung neoplasm; recurrence; small cell; survivors; treatment outcome
Abbreviations: CAPO=cyclophosphamide, doxorubicin, procarbazine, vincristine; CMC/VAP=cyclophosphamide, methotrexate, lomustine (CCNU)/vincristine, doxorubicin, procarbazine; EORTC=European Organization for Research and
Treatment of Cancer; EP=etoposide/cisplatin; NCI= National Cancer Institute; SCC=small cell cancer; SCLC= small cell
lung cancer; SWVOG=Southwest Oncology Group
Small cell lung cancer (SCLC) represents approximately 20% of all lung cancers.' Fifteen to 25% of
patients with limited-stage SCLC and up to 3% of patients with extensive-stage disease will be alive and
cancer free 2 years after treatment with combination
chemotherapy.'13 Approximately one third of these
patients will suffer a relapse with SCLC after 2 years.4-6
*From the National Cancer Institute, Navy Medical Oncology
Branch (Drs. Kelley and Johnson), Biostatistics and Data Management Section (Dr. Venzon), National Cancer Institute; Department of Pathology (Dr. Williams), Department of Medicine
Chute and Roberts), National Naval Medical Center; and the
Uniformed Services University of the Health Sciences (Drs. Chute
and Roberts), Bethesda, Md.
The opinions and assertions contained herein are the expressed
views of the authors and are not to be construed as official or as
reflecting the views of the Department of the Navv or the
Department of Defense.
Reprint requests: Dr. Johnson, National Cancer Institute, Navy
Medical Oncology Branch, Building 8, Room 5101, National Naval
Medical Center, B3ethesda, MD 20889-5105
MDrs.
There are relatively little data on the results of subsequent treatment of these patients.
A prior report in 1983 of 6 patients from this institution described the initial experience with retreatment of patients surviving SCLC for 2 or more years.
Four of the 6 patients retreated with combination
chemotherapy had a partial or complete response and
achieved a median survival of 10 months from the start
of retreatment.7 This success in retreatment is in contrast to the experience with patients with SCLC whose
cancer relapses shortly after induction therapy in
whom retreatment has been only minimally successful.8'9
Recent studies have shown a higher proportion of
patients treated for limited-stage SCLC survive for 2
or more years. Patients with limited-stage SCLC
treated with etoposide/cisplatin (EP) plus chest radiotherapy have achieved 36 to 56% 2-year survival after
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165
initial treatment.10-14 Therefore, more patients are at
risk for late relapses of SCLC. In addition, most
patients with limited-stage disease have been initially
treated with chemotherapy plus chest radiotherapy
which causes more hematologic toxicity than chemotherapy alone.'15"6 The increased use of combinedmodality therapy will likely reduce a patient's ability to
tolerate retreatment with chemotherapy.
We have identified patients who have redeveloped
small cell cancer (SCC) after surviving cancer free for
2 or more years from their initial treatment. The outcome of all patients who redeveloped SCC has been
followed, including both those who received retreatment and those who did not. The patient characteristics, regimens administered, hematologic toxic reactions encountered, response to therapy, and survival
duration before and after redevelopment of SCC were
determined for each patient.
MATERIALS AND METHODS
Patient Population
Patients with histologically confirmed, previously untreated
SCLC were enrolled on National Cancer Institute (NCI) intramural therapeutic trials between 1973 and 1993. These trials were approved by the Institutional Review Boards at the NCI, National
Naval Medical Center, and the Washington, DC Veterans Administration Medical Center; informed consent was obtained from each
patient. All had primary SCLC with assessable tumor lesions; none
were treated in an adjuvant setting after surgical resection.
Patients underwent assessment of disease sites and were classified as having either limited- or extensive-stage disease as previously
defined.'7 18 Initial sites of SCLC were identified as previously described.3 Patients received treatment with combination chemotherapywith orwithout radiotherapywith a variety of regimens that have
been previously reported.17 23 The response to treatment and current status of all patients were determined.
Retreatment of Patients With Redevelopmiwnt of SCC
Patients surviving for 2 years or longer without evidence of cancer were identified. The patients' characteristics at the time of redevelopment of SCC and duration from initial chemotherapy
treatment were obtained from the patients' records. The time to
redevelopment was measured from the start of chemotherapy to the
date of histologic documentation of redevelopment of SCC. The
doses of chemotherapy agents used at the time of redevelopnment
of SCC, doses of chest radiotherapy, and hematologic toxicity of
retreatment were obtained through review of patient records.
Toxicity during retreatment was measured using the NCI common
toxicity criteria.24 The response to retreatment was assessed as
previously described.'6
The survival after redevelopment of SCC wvas measured from the
date of redevelopment of cancer in all patients. Survival curves were
constructed using the method of Kaplan and Meier.25 The p value
for the comparison of survival duration between patients retreated
with etoposide-containing regimens and those who did not receive
etoposide is derived from the likelihood ratio test of the Cox proportional hazards model.26 The p value for the comparison of
response rates in retreated patients is derived from Fisher's exact
test.27 The measured times to redevelopment of SCC were
logarithmically transformed before analysis in order to make their
distribution more uniform.
RESULTS
Patient Characteristics at Initial Diagnosis
Five hundred ninety-four patients with SCLC were
consecutively enrolled on therapeutic trials between
1973 and 1993. The median potential follow-up period
of the 594 patients was 14.8 years and the minimum
follow-up was 2 years.
Sixty-five patients (11%) were alive and free of cancer 2 years after the initiation oftherapy. The other 529
patients died or had suffered relapses with SCLC before 2 years. Twenty of the 65 patients (31%) who
survived cancer free for 2 years from initial diagnosis
redeveloped SCC 2.0 to 12.2 years (median, 3.4 years)
after initiation of therapy for SCLC (Table 1). Among
these 20 patients, there were 11 men and 9 women.
The median age of these patients was 59 years (range,
35 to 69 years). Fifteen patients had limited-stage
SCLC and five had extensive-stage disease after initial
staging evaluation. Chemotherapy administered to the
patients after initial diagnosis of SCLC was cyclophosphamide, methotrexate, lomustine (CCNU)/vincristine, doxorubicin, procarbazine (CMC/VAP) in seven
patients, cyclophosphamide, doxorubicin, procarbazine, vincristine (CAPO) in two, cyclophosphamide,
doxorubicin, vincristine (CAV) in five, and EP in six
patients (Table 1). Fourteen of the 15 patients with
limited-stage disease were treated with chest radiotherapy as part of induction therapy. Initial response
assessment showed a complete response in all 20 patients.
Patient Characteristics at the Time of
Rledevelopnwnt of SCC
The median age of the 20 patients at the time of
redevelopment of SCC was 63 years (range, 39 to 81
years). Performance status was 0 or 1 in 10 patients, 2
in 5 patients, and 3 or 4 in 4 patients (Table 1). Patient
3 was discovered to have SCC at postmortem examination and was scored as performance status 5. Only 1
of the 20 patients did not have histologic documentation of redevelopment of SCC.3 This patient redeveloped a mediastinal mass in the same site of previous
cancer and required urgent therapy because of superior vena cava syndrome. The sites of redevelopment
of SCC in each patient have been published previously.3 Nine patients redeveloped SCC in the chest only;
seven patients redeveloped SCC outside the chest, and
four patients developed SCC both within and outside
the chest. Thirteen patients had the equivalent of extensive-stage disease and seven patients had the equivalent of limited disease at the time of redevelopment
of SCC.
Two patients were judged to have second primary
SCCs. Patient 3 developed SCC of the esophagus 5.9
years after the start of treatment, with no other
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Clinical Investigations
Table 1-Characteristics of 20 Patients With SCLC Who Redeveloped SCC After 2 Years of Cancer-Free Survival*
Cancer-Free
Chest
Interval,
RT
yr
12.2
6.2
5.9
5.9
5.8
CMC/VAP
Yes
Yes
No
Yes
Yes
No
5.5
3
3
5
0
3
0
EP
CAPO
CMCNAP
Yes
Yes
Yes
5.4
5.0
4.5
2
1
1
LTD
LTD
LTD
LTD
EXT
EP
CAV
Yes
Yes
Yes
Yes
No
3.5
3.4
3.0
3.0
2.6
0
4
0
2
1
17/37/F
18/55/M
LTD
LTD
LTD
LTD
EP
CAV
CAV
CMCNAP
Yes
Yes
Yes
No
2.6
2.5
2.3
2.1
2
2
2
1
19/42/M
20/50/F
LTD
LTD
EP
EP
Yes
Yes
2.1
2.0
1
1
Pt No/Age,
yr/Sex
Stage
at Dx
1/69/M
2/57/M
3/60/M
4/60/M
5/65/F
6/63/F
LTD
EXT
7/60/F
8/35/F
9/60/M
LTD
10/62/F
11/52/F
12/50/M
13/66/F
14/57/M
15/60/M
EXT
LTD
LTD
EXT
Initial
Therapy
CAV
CMCNAP
CMCNAP
CMC/VAP
CAV
PS at
Relapse
Treatment
at Relapse
EP'xl cycle
None
None
None
CAV+x2 cycles
EP§x6 cycles+chest RT
Response
NE
NR
CR
Survival
From Relapse,
mo
4
2
0
2
4
46
60 Gy
16/40/M
EXT
LTD
CMCNAP
EP
CAPO
*Pt=patient; Dx=diagnosis; RT=radiation therapy; PS=performance status;
Carbo/E1l x3 cycles
CMC$ xl cycle
CMCI x4
cycles + IE"x6 cycles
Anti-GRP+EP5x6 cycles
CAV*xI cycle
Lobectomy
Abdomen RT 40 Gy
CMClx2 cycles +
CM11x8 cycles
PR
NR
CR
7
26
CR
NR
PR
NR
PR
14
1
14
7
13
4
0
None
CAVt x5 cyclesNR
CAVy x4 cycles
Ettx2 cycles+chest RT
40 Gy
EP5 x4 cycles
EP§x4 cycles+C/Carbo
/E§§x6 cycles
4
PR
NR
4
1
PR
PR
7
15
LTD=limited; EXT=extensive; CAV=cyclophosphamide, doxorubicin,
vincristine22; Carbo=carboplatin; I=ifosfamide; GRP=gastrin-releasing peptide; NE=not evaluable; CR=complete response; PR=partial response;
NR=no response.
tCisplatin, 75 mg/M2 day 1/etoposide, 100 mg/M2 day 1 to 3 every 21 days.
+Cyclophosphamide, 1 g/m2 day 1/doxorubicin, 40 mg/i2 day 1/vincristine, 2 mg day 1 every 21 days.
5Cisplatin, 80 mg/M2 day 1/etoposide, 80 mg/M2 day I to 3 every 21 days.
"Carboplatin, 300 mg/M2 day 1/etoposide, 100 mg/M2 day 1 to 3 every 21 days.
ICyclophosphamide, 1 g/m2 day 1/methotrexate, 15 mg/M2 po x4 doses/lomustine (CCNU), 100 mg/M2 po day 1 every 6 weeks.
**Ifosfamide, 240 mg/mr2 day 1,3,5/etoposide, 125 mg/M2 dayl,3,5 every 21 days.
ItCyclophosphamide, 500 mg/m2 day I/methotrexate, 10 mg/m2 pox4 doses every 21 days.
'tEtoposide, 250 mg/i2 day I to 3.
§§Cyclophosphamide, 750 mg/M2 day 1/carboplatin, 150 mg/M2 day l/etoposide, 80 mg/M2 day 1 to 3 every 21 days.
evidence of SCC at postmortem examination. Patient
4 redeveloped SCLC in the contralateral lung without
evidence of recurrence in the original site 5.9 years
after the start of treatment.3
Patient Treatment at the Time of Redevelopment of
scc
Patients were treated with a variety of regimens and
modalities after redevelopment of SCC (Table 1). The
median duration from the time of diagnosis of redevelopment of SCC to the start of retreatment was 4.9
days (range, 0 to 22 days). Sixteen of the 20 patients
(80%) were retreated at the time of redevelopment of
disease while 4 were not. Eleven patients were retreated with chemotherapy alone, one with abdominal
radiotherapy alone, and two patients with combined
chemotherapy and chest radiotherapy. One patient
underwent a lobectomy after redevelopment of cancer
with both diagnostic and therapeutic intent. An addi-
tional patient was treated with a monoclonal antibody
directed against the autocrine growth factor, gastrinreleasing peptide, as previously described.28 Four patients received no further antitumor therapy: one
patient had relapse documented at postmortem examination, one patient had performance status 3 and did
not receive retreatment, and two patients with performance status less than 2 declined further treatment
(Table 1).
Nine of the 16 patients (56%) who received treatment at the time of redevelopment of SCC had an
objective tumor response: 3 complete and 6 partial.
Seven of 13 patients (57%) who received chemotherapy with or without radiotherapy responded (2 complete and 5 partial). The patient treated with the
monoclonal antibody directed against gastrin-releasing
peptide also achieved a complete response. This
patient subsequently received 6 cycles of EP chemotherapy that maintained a response for 10 months.
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167
z
70
> 60
C
50
Z
40
LCL
30
_
20
10
10
0
1
2
3
4
YEARS AFTER RELAPSE
FIGURE 1. Survival of patients from the time of redevelopment of
SCC. The curve represents the survival of all patients after the redevelopment of SCLC.
We also analyzed patients with performance status
0 to 2 at the time of redevelopment of SCLC because
these criteria are typically used as entry requirements
for clinical trials for patients with newly diagnosed
SCLC. 10"1318 Among these patients with a performance status of 0 to 2 who received retreatment, 9 of
13 (69%) had a partial or complete response to therapy. None of the patients whose performance status
was greater than 2 had an objective tumor response
following retreatment.
Ten patients were treated with a chemotherapy
regimen at the time of redevelopment of SCLC which
contained one or more drugs that they had received
previously (Table 1). Six of these 10 patients (60%)
responded to retreatment. Six patients were treated
with the identical chemotherapy regimen at the time
of redevelopment of SCLC which they had received at
the time of initial diagnosis and three of these patients
had a partial response. Eight patients were treated with
an etoposide-containing regimen with or without cisplatin at redevelopment of SCLC and 6 of 8 (75%)
responded (2 complete response, 4 partial response).
Three of the 8 patients (38%) not retreated with an
etoposide-based regimen had a response (3 partial response).
The median survival after redevelopment of SCC of
all 20 patients, including those who did not receive
retreatment, was 3.9 months (range, 0 to 46 months)
(Fig 1). Six ofthe 20 patients (30%) survived more than
1 year from the time of redevelopment of SCLC, and
2 patients (10%) survived more than 2 years beyond the
date of redevelopment. One of these 2 patients died
from recurrent SCLC 26 months after treatment at
relapse and the other patient remained without evidence of SCLC at the time of her death from bacterial peritonitis 46 months later (Fig 2).
The median survival from the time of redevelop-
ment of SCLC of the 16 patients who were retreated
was 6.5 months (range, 1 to 46 months). Analysis of
survival based on patient response reveals that the
median survival of the 3 patients who achieved complete response was 26 months; the median survival of
the 6 patients who achieved partial response was 10
months; and the median survival of those 7 patients
who had no response to retreatment was 4 months.
The median survival ofthe 13 patients who received
chemotherapy with or without radiotherapy was 4.4
months (range, 1 to 46 months). The median survival
of the 15 patients with performance status 0 to 2, including three patients who were not retreated, was 7.2
months.
Analysis of patients based on the retreatment regimen received shows that the 8 patients retreated with
etoposide-based chemotherapy had a median survival
of 11 months and the 8 patients who received nonetoposide-based treatment (including radiation and
surgery) had a median survival of 5.5 months (p=0.056).
Seven of 13 patients (54%) who received chemotherapy developed grade 4 or 5 leukopenia from reinduction therapy at the time of redevelopment of
SCLC. Two of the 13 patients (15%) who underwent
retreatment died from infections that were directly
related to treatment-induced neutropenia. Six of the 7
patients (86%) who developed grade 4 or 5 hematologic toxicity during retreatment had received combined modality therapy during their initial treatment of
SCLC. Two patients developed grade 3 leukopenia
during retreatment and the remaining 4 patients had
no hematologic toxicity greater than grade 2. Neutrophil counts were not routinely calculated in all patients.
Sixteen of the 20 patients who redeveloped SCC 2
or more years after initial diagnosis died of SCLC. Two
patients died from intercurrent infection during the
treatment of relapse; one patient died from organic
brain syndrome and was found to have SCC in the
esophagus at postmortem examination; one patient
died from peritonitis 46 months after relapse and had
no evidence of SCLC at autopsy.
DISCUSSION
Patients who have had late redevelopment of SCC
(>2 years from initial diagnosis) can respond to retreatment with chemotherapy and prolonged survival
can be achieved. The median survival duration of 7.2
months after redevelopment of SCC in patients with
performance status 0 to 2 is approaching that of
patients with extensive-stage SCLC and similar functional capacity when measured from the time of initial
therapy." 29 The 1-year and 2-year survival probabilities
of 30% and 10% in our population of patients who redeveloped SCLC is similar to the 1- and 2-year survival
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Clinical Investigations
FIGURE 2. Chest radiographs and CT scans of the chest of a patient who obtained prolonged remission
following retreatment of SCLC. A, chest radiograph at the time of redevelopment of SCLC that demonstrates lesion in the left lingula (arrow). B, chest radiograph following four cycles of EP chemotherapy
demonstrating resolution o abnormality. C, chest radiograph 23 months later demonstrating persistent
absence of SCLC. D, chest CT scan showing the left lingular mass at the time of redevelopment of SCLC.
E, chest CT scan showing resolution of the left lingular tumor following retreatment with chemotherapy.
probabilities for initially treated patients with both
limited- and extensive-stage SCLC."12
It has been suggested previously that the duration of
first response to chemotherapy for SCLC is a predictor of the outcome of retreatment at the time of
relapse.9 We have examined the Southwest Oncology
Group (SWOG) experience in retreating 67 patients
with SCLC who suffered relapses or progressed within
a median time of 6 weeks (range, 3 to 28 weeks) from
the completion of induction chemotherapy. Forty-six
of 67 patients (69%) were initially treated with regimens containing EP, and 21 (31%) were treated with
other chemotherapy regimens. Twenty-seven patients
(39%) were initially treated with combination chemotherapy and chest radiotherapy. Only 3 of the 67 (4%)
patients retreated with cyclophosphamide-based chemotherapy at the time of relapse in this study achieved
an objective response. The median survival from the
start of retreatment for this group was 10 weeks.8 The
patients were in poor physical condition because nearly
half of the patients (46%) in the SWOG study had a
performance status of 2 to 4 at the time of relapse. A
European Organization for Research and Treatment of
Cancer (EORTC) study also examined the outcome of
18 patients with performance status 0 to 3 who suffered
relapses with SCLC after a median initial response of
less than 34 weeks following treatment with cyclophosphamide, doxorubicin, and etoposide. In this
study, 8 of 18 patients (44%) had an objective response
to retreatment with cyclophosphamide, doxorubicin,
and etoposide and the median survival from the start
of retreatment was 17 weeks.9 Comparison of these
three treatment groups is difficult given the differences
in performance status and treatment regimens in each
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group. Although the response rate in our retreated
patients is higher than the response rate in the SWOG
cohort (NCI 56% vs SWOG 4%; p<0.0001), it is not
significantly different than the EORTC cohort (NCI
56% vs EORTC 44%; p=0.73). The median survival in
each group of retreated patients does not appear to be
significantly different (NCI 6.7 months vs SWOG 2.5
months vs EORTC 4.2 months). A direct statistical
comparison of the survival duration of these three cohorts cannot be done since we have extracted the
SWOG and EORTC results from published articles
and the individual patient data from these studies are
not available.8'9
The objective tumor response after retreatment of
late redevelopment of SCLC with agents previously
utilized during initial therapy is similar to the experience in salvage therapy of Hodgkin's disease.30 Fourteen of 19 patients (74%) with Hodgkin's disease described by Longo et al30 who suffered relapses greater
than 1 year from initial diagnosis responded to the
identical chemotherapy regimen they had received
during initial treatment. The survival duration in these
patients was significantly longer than the survival duration of patients with Hodgkin's disease who suffered
relapses less than 1 year from initial diagnosis.30 Similarly, in patients with SCLC who have redeveloped
their disease more than 2 years from initial diagnosis,
7 of 13 patients (54%) who were retreated with
chemotherapy achieved a partial or complete response.
The median survival of 7.2 months among the patients
with good performance status who redeveloped SCLC
demonstrates that prolonged survival can be achieved
in those patients who can tolerate the treatment. Our
experience in retreating patients with late redevelopment of SCC is similar to the experience in retreating
late relapses ofbreast cancer and multiple myeloma, in
which prolonged survival has also been reported
following retreatment.31'32
The hematologic toxicity of salvage chemotherapy in
patients who have had late redevelopment of SCLC is
significant. Grade 4 or 5 leukopenia occurred in 7 of
the 13 patients (54%) who we have retreated with
chemotherapy more than 2 years from initial diagnosis. This incidence of myelotoxicity is higher than what
was seen in a recent SWOG trial of relapsed patients
with SCLC who were retreated within a median of 6
weeks from prior chemotherapy. In the SWOG study,
20 of 67 patients (30%) retreated with cyclophosphamide/cytarabine/vincristine after early relapse developed grade 4 neutropenia. Twenty-six of the 67
patients (39%) in the SWOG study had receivedgrior
combined chest radiotherapy and chemotherapy. Ten
of the 13 patients (77%) we have retreated with chemotherapy at the time of redevelopment of SCC had
previously received combined modality therapy. The
higher proportion of patients treated with combined
chemotherapy and chest radiotherapy may account for
the higher incidence of hematologic toxicity we have
seen in our patients compared with the patients
described by SWOG. For further comparison, in our
most recently completed trial of standard-dose EP for
patients with newly diagnosed extensive-stage SCLC,
initial induction chemotherapy produced grade 4 leukopenia in only 1 of 46 patients (2%).'7 Combined
modality therapy for SCLC causes increased bone
marrow toxicity.15 Therefore, it is not surprising for
these patients to develop severe hematologic toxic reactions at the time of retreatment, even 2 years
following initial therapy. Although patients with late
redevelopment of their SCC may continue to have
disease that responds to chemotherapy, their ability to
tolerate conventional doses of chemotherapy is likely
reduced, particularly those patients who have previously received combined modality therapy.
Two-year survivors of SCLC who redevelop SCLC
appear to respond to repeated administration of chemotherapy at a higher rate than patients with earlier
redevelopment of the disease. As seen in patients with
Hodgkin's disease, the tumor response to retreatment
in patients with late redevelopment of SCC is generally less impressive and shorter in duration than the
initial response to therapy at first diagnosis. The short
median survival in patients who redevelop SCLC is
most likely because the disease is more often recurrent
rather than a second primary cancer. We have previously shown that the 18 patients who developed
recurrent SCLC followed a typical pattern of recurrence.3 Seven re-presented with cancer in the initial
lobe plus regional lymph nodes, five in the initially involved lymnph nodes plus distant sites, and six in distant
sites alone. We believe that the recurrence of SCLC
represents a regrowth of residual SCLC cells that took
place after chemotherapy was discontinued. We hypothesize that the regrowth of the tumor over this period of time has allowed a redevelopment of tumor
heterogeneity so a significant proportion of the SCLC
cells are once again sensitive to readministration of
combination chemotherapy. Therefore, many of our
patients have had a tumor response after retreatment.
The data presented herein and the data from the
literature allow us to make the following recommendations: patients with a performance status of 0 to 2
who redevelop SCLC 2 or more years after initial
treatment should be retreated with combination chemotherapy. Certain patients, especially those previously treated with combined modality therapy, are
likely to develop grade 3 and 4 hemnatologic toxic
reactions. Therefore, we recommend that physicians
initially use chemotherapy regimens that are unlikely
to cause severe hematologic toxicity.
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Clinical Investigations
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