Adjuvant Nitrosourea Therapy for Glioblastoma Ronald
Brisman, MD; Edgar M. Housepian, MD; Chu Chang, MD; Philip Duffy, MD; Eugene Balis, MD
\s=b\ An attempt was made to evaluate the potential advantages of chemotherapy in the treatment of 62 patients with glioblastoma. Twenty-four of the 62 patients received adjuvant nitrosourea chemotherapy with carmustine (BCNU), lomustine (CCNU), or semustine (methyl CCNU) in addition to surgery and radiotherapy. Thirty-three of the 62 patients were involved in a controlled, prospective, randomly allocated study. Quality or quantity of survival was not prolonged in patients who received chemotherapy. Age greater than 64 years, a severe postoperative neurological deficit, or the onset of symptoms less than 12 months prior to
associated with a worse The valid evaluation of the effect of a form of treatment on survival in patients with glioblastoma is contingent on the rigorous avoidance of preselected factors that may predispose the treated group to a more favorable prognosis. (Arch Neurol 33:745-750, 1976)
surgery
were
prognosis.
(150 mg/sq m)
was
weeks. When
An internal decompression done when the tumor was in a nonvital area and it was believed that this could be done without worsening neurological func¬ tion. Reoperation was performed in 15 patients for tumor recurrence when the patient had a functionally useful remission for at least ten months after the initial surgery. No patient had more than two craniotomies. Within four weeks after surgery (usually within ten days), random¬ ization to either x-ray therapy alone or x-ray therapy plus chemotherapy was offered to patients who appeared likely to survive the six-week period required for radiotherapy. Not all patients who qual¬ ified were willing to be randomized. Informed consent was obtained in each case after risks and possible benefits of the study protocol and alternative forms of treatment were explained to the patient and the responsible relatives. For those patients who consented to randomization (33 cases), the anticipated treatment modality of radiotherapy alone (16 cases)
radiotherapy plus chemotherapy (17 cases) was determined by a sealed envelope technique. Not all of the randomized or
and clinical studies sug¬ gest that the lipid-soluble nitro¬ soureas (carmustine [BCNU], lomus¬ tine [CCNU], and semustine [methyl CCNU] ) may be effective in the treatment of malignant brain tu¬ mors'" We have evaluated this sug¬ gestion since 1970 in a prospective, controlled, randomly allocated clinical
Laboratory
study.
SUBJECTS AND METHODS The study included 62 consecutive patients, with verified glioblastoma (Kernohan grade 3 or 4) for which a diagnosis was made and biopsy specimen obtained for the first time between Jan 1, 1970, and Dec 31,1972, without prior radiotherapy or
Accepted
for publication March 9, 1976. From the Brain Tumor Study Group, College of Physicians and Surgeons, Columbia University, and the New York Neurological Institute, Columbia Presbyterian Medical Center. Other members of the Study Group are listed on p 750. Reprint requests to Neurological Institute, 710 W 168th St, New York, NY 10032 (Dr Brisman).
once every six to eight leukopenia (white blood cells [WBCs] < 3,200/cu mm) or thrombocyto¬ penia (platelets < 75,000/cu mm) devel¬ oped, the subsequent chemotherapy was reduced to two thirds of the original dose. Chemotherapy was stopped when the
chemotherapy.
patients received a full course of radio¬ therapy because of rapid clinical deteriora¬ tion. A full course of radiotherapy consisted of 3,000 rads to the whole brain in three weeks, followed by an additional 3,000 rads to the tumor; a cobalt 60 unit was used. Radiotherapy was initiated within four weeks (usually ten days) of surgery. Twelve patients who did not receive
chemotherapy were given hyperbaric ox¬ ygen during the last 3,000 rads of their radiotherapy. Nitrosourea chemotherapy started within four weeks of surgery ten days) in patients who were randomized to receive this adjuvant form of treatment. Patients with glioblastoma who began chemotherapy in 1970 were given carmus¬ tine intravenously (100 mg/sq m) daily for two days, which was repeated every six to eight weeks. Those who started chemo¬ therapy in 1971 received an orally adminis¬ tered dose of lomustine (100 mg/sq m) once every six to eight weeks. When chemo¬ therapy was initiated in 1972, semustine, which had a superior effect against certain animal tumor models,12 was given orally was
(usually
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illness became terminal. Patients who received chemotherapy had a complete blood cell count and platelet count each week. Every eight weeks the following laboratory determinations were obtained: calcium, inorganic phosphorous, glucose, urea nitrogen, uric acid, cholester¬ ol, total protein, albumin, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and glutamic oxaloacetic transaminase. Skull x-ray films, echoencephalogram, electroencephalogram, and brain scan (mercury 197) were performed on all patients every 16 weeks, or earlier if clin¬ ical deterioration occurred. Patients were seen every six to eight weeks, and a complete neurological examination and functional status evaluation were done at that time. Survival was determined from the day of tissue diagnosis of glioblastoma to death. Patients were divided into three groups for
analysis. Group
A
(62 patients) represents
the entire consecutive series of tissueverified glioblastoma; 22 of these patients did not complete a full course of radiother¬ apy. Group (40 patients) includes those who had surgery and completed a full course of radiotherapy (6,000 rads, except two patients who received 5,080 and 5,400 rads) that was started within four weeks (usually ten days) of surgery. Group C (33 patients) is comprised of those who were randomized soon after surgery to receive either chemotherapy and radiotherapy (17 patients) or radiotherapy alone (16 pa¬ tients). When group C results were tabu¬ lated, a patient was considered to be in the original treatment group to which he or she was randomized, whether or not a full course of that treatment was given. Thus, not all patients in group C received a full course of radiotherapy, and of those who were randomized to receive radiotherapy and chemotherapy, four did not receive chemotherapy because of a rapidly deterio¬ rating clinical condition. A separate anal¬ ysis was done on these patients who were
SURVIVAL 1970-1972
GLIOBLASTOMA
GLIOBLASTOMA SURVIVAL COMPLETED RADIOTHERAPY
» _
CHEMOTHERAPY 23 patients
CHEMOTHERAPY 19 patients
^
NO CHEMOTHERAPY 21
b—< c,
>*w
«a NO CHEMOTHERAPY 39
patients
3
6
_L _J _L _L _L _L 12 15 18 21 24 27 6 9 MONTHS after SURGERY 2—Survival data for group glioblastoma patients. All Fig patients completed at least 5,000 rads of radiotherapy.
9
randomized and who completed a full of radiotherapy (12 patients) or a full course of radiotherapy and at least one course of chemotherapy (12 patients). course
RESULTS
Group Of
A
consecutive series of 62 with patients glioblastoma, 50% lived for more than 5.4 months. Six (9.7%) were alive more than two years after initial surgery (Pig 1). One of these patients had received radiotherapy and chemotherapy (Semustine, 150 mg/sq m every six to eight weeks for four courses and 100 mg/sq m every six to eight weeks for ten courses) and was reoperated on for recurrent tumor 26 months after initial surgery; he died four months later. Five of the other long-term survivors had been treated by surgery and radiotherapy alone without adjuvant chemother¬ apy. One of these patients, a 7-yearold boy, was living and well without evidence of recurrence 31 months after initial surgery. Two men were reoperated on for a cystic recurrence at 16 and 35 months after primary surgery and were still alive with mild neurological deficit 34 and 36 months after initial tissue diagnosis. Two a
>>-- o
-\ " -~o
12 15 18 21 24 27 30 MONTHS after SURGERY Fig 1.—Survival data for group A glioblastoma patients. False impression of benefit from chemotherapy obtained because many patients with poor prognosis were not given chemotherapy. 0
patients
other
men were
_L
O
alive without clinical
at 33 and 34 months after initial surgery. recurrence
In group A, there were 23 patients who received chemotherapy; 50% lived for more than 12 months, and one (4%) survived for more than 24 months (Fig 1). Thirty-nine patients did not receive chemotherapy; 50% lived more than 4.2 months, and five (13%) survived for more than 24 months. An analysis of other factors that might have influenced survival showed three patients who were at least 65 years old and three patients with a severe neurological deficit (7 to 14 days after surgery) in the chemotherapy group; there were 15 patients who were at least 65 years old, and 18 with a severe postoperative deficit in the nonchemo-
therapy group (Table 1). Group
B:
Nineteen
glioblastoma patients completed a full course of radio¬ therapy were also given chemother¬ apy; 50% were alive after 12 months, and one (5%) survived for more than 24 months (Fig 2). There were 21 patients who completed radiotherapy, but did not receive chemotherapy; 50% were living after nine months, and who
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five (24%) were alive after 24 months. These differences in survival, as well as differences in quality of survival (Tables 2 and 3) between the chemo¬ and therapy nonchemotherapy groups, are not significant to the .05 level. There were a few more patients who were older than 64 years (five patients) in the nonchemothera¬ py than in the chemotherapy group (three patients) (Table 1). There were more patients with onset of symptoms at least 12 months prior to surgery (six patients) in the nonchemotherapy group than in the chemotherapy group =
(three patients).
Group C Seventeen patients were random¬ ized to receive chemotherapy in addi¬ tion to surgery and radiotherapy. Three of these patients died before they were able to complete a full course of radiotherapy. Two of these patients who were very ill after randomization and a third patient, who completed 5,400 rads of radio¬ therapy but had an unexplained fever,
given chemotherapy, even though they were randomized to receive it. Four patients who were randomized to radiotherapy alone were never
Table 1.—Factors That
Group
Might
Influence Survival
A
Group
Chemo¬
chemo¬
Chemo¬
Non¬ chemo¬
Chemo¬
Non¬ chemo¬
therapy (N = 23)
(N
therapy = 39)
therapy (N = 19)
therapy (N = 21)
therapy (N = 17)
therapy (N = 16)
51
62
51
56
49
56
5-70
15 7-78
16-70
7-73
16-73
31-69
16
26
13
11 10
13
10
13
13
17
16
10
10
15
Non¬
Age Median, yr No. of patients aged Range, yr
65 yr
Sex No. of male patients No. of female patients No. of patients randomized for
therapy
Group C
13 14
Onset of symptoms Median, mo prior to surgery No. of patients with onset 12 mo prior to surgery No. of
patients with severe neurological deficit* Histological grade No. of patients with grade 3 No. of patients with grade 4 No. of patients with large decompression No. of operations performed! No. of patients receiving 6,000 rads No. of patients receiving O, No. of patients receiving carmustine No. of patients lomustine No. of patients semustine
14
22
19 26
27 41
15 22
23
12 20
18
21
20Î
19
21Î
14§
12
12
12
receiving receiving
6
'First week after surgery. tNo patient had more than two craniotomies. JOne patient received 5,400 rads; one received 5,080 rads. SOne patient received 5,400 rads. |Four patients who were randomized to receive chemotherapy did not receive it because of rapidly deteriorating clinical
unable to complete a full course radiotherapy. There was no differ¬ ence (P > .3) in quantity or quality of
were
Table
of
survival between those randomized to receive chemotherapy (50% alive after 6.1 months) and those randomized not to receive chemotherapy (Fig 3) (50% alive after 6.3 months, Tables 2 and 3). There were a few more patients (five patients) with a long preoperative symptom period in the nonchemo¬ therapy subgroup than in the chemo¬
therapy subgroup (two patients) (Ta¬ ble 1). Of the 12 patients who were randomized to radiotherapy alone and who completed a full course of radio¬ therapy, 50% were alive after 9.1 months. This was not significantly different (P > .3) from the other 12 patients who were randomized and who completed a full course of radio¬ therapy and at least one course of chemotherapy; 50% of these patients were
alive after
seven
months.
2.—Chemotherapy
and Survival
Total No. of Patients
Group A Chemotherapy Nonchemotherapy Group Chemotherapy Nonchemotherapy Group C Chemotherapy Nonchemotherapy
course.
50% Sur¬
vival,
23
mo
12.0 4.2
-C.005
39
>300
19
12.0
21
9.0
16
6.3
.175t
' 'Based on standardized Wilcoxin statistical test. a negative Wilcoxin statistic.
tAssociated with
Factors That Might Influence Survival Several factors were analyzed to
was associated (P < .05) with shorter survival. The size of opera¬ tive resection, histological grade (3 or 4), or sex did not correlate with survi¬ val.
surgery a
see
if they correlated with prolonged survival (Table 4). A severe neurolog¬ ical deficit that was present between 7 and 14 days after surgery, patient age greater than 64 years, or the onset of symptoms less than 12 months before
Downloaded From: http://archneur.jamanetwork.com/ by a University of Victoria User on 06/05/2015
Toxicity (Group B) All sourea
patients who received nitrochemotherapy showed either
3.—Quality
Table
of Survival
No.(%) Group
Chemotherapy (N = 23)
Good Survival* > 6 mo >12mo
A
Group C
Group
Nonchemotherapy
Chemotherapy (N = 19) 10(53) 7(37)
(N = 39) 9(23) 7(18)
11(48) 7(30)
of Patients
Nonchemotherapy (N = 21) 10(48) 7(33)
Chemotherapy (N 17) 7(41) 6(35) =
Nonchemotherapy (N = 16) 6(38) 5(31)
_>18 mo_2( 9)_5(13)_2(11)_5(24)_2(12)_4(25)_ >24 1( 4)
mo
"Functioning
at
Table
a
normal
or near
normal
5(13)
1( 5)
4.—Probability of Significance of
Factors
Factors
Total No. of Patients
Severe neurological deficitf Present Absent
Affecting
:65 yr
Brisman, MD; Edgar M. Housepian, MD; Chu Chang, MD; Philip Duffy, MD; Eugene Balis, MD
\s=b\ An attempt was made to evaluate the potential advantages of chemotherapy in the treatment of 62 patients with glioblastoma. Twenty-four of the 62 patients received adjuvant nitrosourea chemotherapy with carmustine (BCNU), lomustine (CCNU), or semustine (methyl CCNU) in addition to surgery and radiotherapy. Thirty-three of the 62 patients were involved in a controlled, prospective, randomly allocated study. Quality or quantity of survival was not prolonged in patients who received chemotherapy. Age greater than 64 years, a severe postoperative neurological deficit, or the onset of symptoms less than 12 months prior to
associated with a worse The valid evaluation of the effect of a form of treatment on survival in patients with glioblastoma is contingent on the rigorous avoidance of preselected factors that may predispose the treated group to a more favorable prognosis. (Arch Neurol 33:745-750, 1976)
surgery
were
prognosis.
(150 mg/sq m)
was
weeks. When
An internal decompression done when the tumor was in a nonvital area and it was believed that this could be done without worsening neurological func¬ tion. Reoperation was performed in 15 patients for tumor recurrence when the patient had a functionally useful remission for at least ten months after the initial surgery. No patient had more than two craniotomies. Within four weeks after surgery (usually within ten days), random¬ ization to either x-ray therapy alone or x-ray therapy plus chemotherapy was offered to patients who appeared likely to survive the six-week period required for radiotherapy. Not all patients who qual¬ ified were willing to be randomized. Informed consent was obtained in each case after risks and possible benefits of the study protocol and alternative forms of treatment were explained to the patient and the responsible relatives. For those patients who consented to randomization (33 cases), the anticipated treatment modality of radiotherapy alone (16 cases)
radiotherapy plus chemotherapy (17 cases) was determined by a sealed envelope technique. Not all of the randomized or
and clinical studies sug¬ gest that the lipid-soluble nitro¬ soureas (carmustine [BCNU], lomus¬ tine [CCNU], and semustine [methyl CCNU] ) may be effective in the treatment of malignant brain tu¬ mors'" We have evaluated this sug¬ gestion since 1970 in a prospective, controlled, randomly allocated clinical
Laboratory
study.
SUBJECTS AND METHODS The study included 62 consecutive patients, with verified glioblastoma (Kernohan grade 3 or 4) for which a diagnosis was made and biopsy specimen obtained for the first time between Jan 1, 1970, and Dec 31,1972, without prior radiotherapy or
Accepted
for publication March 9, 1976. From the Brain Tumor Study Group, College of Physicians and Surgeons, Columbia University, and the New York Neurological Institute, Columbia Presbyterian Medical Center. Other members of the Study Group are listed on p 750. Reprint requests to Neurological Institute, 710 W 168th St, New York, NY 10032 (Dr Brisman).
once every six to eight leukopenia (white blood cells [WBCs] < 3,200/cu mm) or thrombocyto¬ penia (platelets < 75,000/cu mm) devel¬ oped, the subsequent chemotherapy was reduced to two thirds of the original dose. Chemotherapy was stopped when the
chemotherapy.
patients received a full course of radio¬ therapy because of rapid clinical deteriora¬ tion. A full course of radiotherapy consisted of 3,000 rads to the whole brain in three weeks, followed by an additional 3,000 rads to the tumor; a cobalt 60 unit was used. Radiotherapy was initiated within four weeks (usually ten days) of surgery. Twelve patients who did not receive
chemotherapy were given hyperbaric ox¬ ygen during the last 3,000 rads of their radiotherapy. Nitrosourea chemotherapy started within four weeks of surgery ten days) in patients who were randomized to receive this adjuvant form of treatment. Patients with glioblastoma who began chemotherapy in 1970 were given carmus¬ tine intravenously (100 mg/sq m) daily for two days, which was repeated every six to eight weeks. Those who started chemo¬ therapy in 1971 received an orally adminis¬ tered dose of lomustine (100 mg/sq m) once every six to eight weeks. When chemo¬ therapy was initiated in 1972, semustine, which had a superior effect against certain animal tumor models,12 was given orally was
(usually
Downloaded From: http://archneur.jamanetwork.com/ by a University of Victoria User on 06/05/2015
illness became terminal. Patients who received chemotherapy had a complete blood cell count and platelet count each week. Every eight weeks the following laboratory determinations were obtained: calcium, inorganic phosphorous, glucose, urea nitrogen, uric acid, cholester¬ ol, total protein, albumin, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and glutamic oxaloacetic transaminase. Skull x-ray films, echoencephalogram, electroencephalogram, and brain scan (mercury 197) were performed on all patients every 16 weeks, or earlier if clin¬ ical deterioration occurred. Patients were seen every six to eight weeks, and a complete neurological examination and functional status evaluation were done at that time. Survival was determined from the day of tissue diagnosis of glioblastoma to death. Patients were divided into three groups for
analysis. Group
A
(62 patients) represents
the entire consecutive series of tissueverified glioblastoma; 22 of these patients did not complete a full course of radiother¬ apy. Group (40 patients) includes those who had surgery and completed a full course of radiotherapy (6,000 rads, except two patients who received 5,080 and 5,400 rads) that was started within four weeks (usually ten days) of surgery. Group C (33 patients) is comprised of those who were randomized soon after surgery to receive either chemotherapy and radiotherapy (17 patients) or radiotherapy alone (16 pa¬ tients). When group C results were tabu¬ lated, a patient was considered to be in the original treatment group to which he or she was randomized, whether or not a full course of that treatment was given. Thus, not all patients in group C received a full course of radiotherapy, and of those who were randomized to receive radiotherapy and chemotherapy, four did not receive chemotherapy because of a rapidly deterio¬ rating clinical condition. A separate anal¬ ysis was done on these patients who were
SURVIVAL 1970-1972
GLIOBLASTOMA
GLIOBLASTOMA SURVIVAL COMPLETED RADIOTHERAPY
» _
CHEMOTHERAPY 23 patients
CHEMOTHERAPY 19 patients
^
NO CHEMOTHERAPY 21
b—< c,
>*w
«a NO CHEMOTHERAPY 39
patients
3
6
_L _J _L _L _L _L 12 15 18 21 24 27 6 9 MONTHS after SURGERY 2—Survival data for group glioblastoma patients. All Fig patients completed at least 5,000 rads of radiotherapy.
9
randomized and who completed a full of radiotherapy (12 patients) or a full course of radiotherapy and at least one course of chemotherapy (12 patients). course
RESULTS
Group Of
A
consecutive series of 62 with patients glioblastoma, 50% lived for more than 5.4 months. Six (9.7%) were alive more than two years after initial surgery (Pig 1). One of these patients had received radiotherapy and chemotherapy (Semustine, 150 mg/sq m every six to eight weeks for four courses and 100 mg/sq m every six to eight weeks for ten courses) and was reoperated on for recurrent tumor 26 months after initial surgery; he died four months later. Five of the other long-term survivors had been treated by surgery and radiotherapy alone without adjuvant chemother¬ apy. One of these patients, a 7-yearold boy, was living and well without evidence of recurrence 31 months after initial surgery. Two men were reoperated on for a cystic recurrence at 16 and 35 months after primary surgery and were still alive with mild neurological deficit 34 and 36 months after initial tissue diagnosis. Two a
>>-- o
-\ " -~o
12 15 18 21 24 27 30 MONTHS after SURGERY Fig 1.—Survival data for group A glioblastoma patients. False impression of benefit from chemotherapy obtained because many patients with poor prognosis were not given chemotherapy. 0
patients
other
men were
_L
O
alive without clinical
at 33 and 34 months after initial surgery. recurrence
In group A, there were 23 patients who received chemotherapy; 50% lived for more than 12 months, and one (4%) survived for more than 24 months (Fig 1). Thirty-nine patients did not receive chemotherapy; 50% lived more than 4.2 months, and five (13%) survived for more than 24 months. An analysis of other factors that might have influenced survival showed three patients who were at least 65 years old and three patients with a severe neurological deficit (7 to 14 days after surgery) in the chemotherapy group; there were 15 patients who were at least 65 years old, and 18 with a severe postoperative deficit in the nonchemo-
therapy group (Table 1). Group
B:
Nineteen
glioblastoma patients completed a full course of radio¬ therapy were also given chemother¬ apy; 50% were alive after 12 months, and one (5%) survived for more than 24 months (Fig 2). There were 21 patients who completed radiotherapy, but did not receive chemotherapy; 50% were living after nine months, and who
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five (24%) were alive after 24 months. These differences in survival, as well as differences in quality of survival (Tables 2 and 3) between the chemo¬ and therapy nonchemotherapy groups, are not significant to the .05 level. There were a few more patients who were older than 64 years (five patients) in the nonchemothera¬ py than in the chemotherapy group (three patients) (Table 1). There were more patients with onset of symptoms at least 12 months prior to surgery (six patients) in the nonchemotherapy group than in the chemotherapy group =
(three patients).
Group C Seventeen patients were random¬ ized to receive chemotherapy in addi¬ tion to surgery and radiotherapy. Three of these patients died before they were able to complete a full course of radiotherapy. Two of these patients who were very ill after randomization and a third patient, who completed 5,400 rads of radio¬ therapy but had an unexplained fever,
given chemotherapy, even though they were randomized to receive it. Four patients who were randomized to radiotherapy alone were never
Table 1.—Factors That
Group
Might
Influence Survival
A
Group
Chemo¬
chemo¬
Chemo¬
Non¬ chemo¬
Chemo¬
Non¬ chemo¬
therapy (N = 23)
(N
therapy = 39)
therapy (N = 19)
therapy (N = 21)
therapy (N = 17)
therapy (N = 16)
51
62
51
56
49
56
5-70
15 7-78
16-70
7-73
16-73
31-69
16
26
13
11 10
13
10
13
13
17
16
10
10
15
Non¬
Age Median, yr No. of patients aged Range, yr
65 yr
Sex No. of male patients No. of female patients No. of patients randomized for
therapy
Group C
13 14
Onset of symptoms Median, mo prior to surgery No. of patients with onset 12 mo prior to surgery No. of
patients with severe neurological deficit* Histological grade No. of patients with grade 3 No. of patients with grade 4 No. of patients with large decompression No. of operations performed! No. of patients receiving 6,000 rads No. of patients receiving O, No. of patients receiving carmustine No. of patients lomustine No. of patients semustine
14
22
19 26
27 41
15 22
23
12 20
18
21
20Î
19
21Î
14§
12
12
12
receiving receiving
6
'First week after surgery. tNo patient had more than two craniotomies. JOne patient received 5,400 rads; one received 5,080 rads. SOne patient received 5,400 rads. |Four patients who were randomized to receive chemotherapy did not receive it because of rapidly deteriorating clinical
unable to complete a full course radiotherapy. There was no differ¬ ence (P > .3) in quantity or quality of
were
Table
of
survival between those randomized to receive chemotherapy (50% alive after 6.1 months) and those randomized not to receive chemotherapy (Fig 3) (50% alive after 6.3 months, Tables 2 and 3). There were a few more patients (five patients) with a long preoperative symptom period in the nonchemo¬ therapy subgroup than in the chemo¬
therapy subgroup (two patients) (Ta¬ ble 1). Of the 12 patients who were randomized to radiotherapy alone and who completed a full course of radio¬ therapy, 50% were alive after 9.1 months. This was not significantly different (P > .3) from the other 12 patients who were randomized and who completed a full course of radio¬ therapy and at least one course of chemotherapy; 50% of these patients were
alive after
seven
months.
2.—Chemotherapy
and Survival
Total No. of Patients
Group A Chemotherapy Nonchemotherapy Group Chemotherapy Nonchemotherapy Group C Chemotherapy Nonchemotherapy
course.
50% Sur¬
vival,
23
mo
12.0 4.2
-C.005
39
>300
19
12.0
21
9.0
16
6.3
.175t
' 'Based on standardized Wilcoxin statistical test. a negative Wilcoxin statistic.
tAssociated with
Factors That Might Influence Survival Several factors were analyzed to
was associated (P < .05) with shorter survival. The size of opera¬ tive resection, histological grade (3 or 4), or sex did not correlate with survi¬ val.
surgery a
see
if they correlated with prolonged survival (Table 4). A severe neurolog¬ ical deficit that was present between 7 and 14 days after surgery, patient age greater than 64 years, or the onset of symptoms less than 12 months before
Downloaded From: http://archneur.jamanetwork.com/ by a University of Victoria User on 06/05/2015
Toxicity (Group B) All sourea
patients who received nitrochemotherapy showed either
3.—Quality
Table
of Survival
No.(%) Group
Chemotherapy (N = 23)
Good Survival* > 6 mo >12mo
A
Group C
Group
Nonchemotherapy
Chemotherapy (N = 19) 10(53) 7(37)
(N = 39) 9(23) 7(18)
11(48) 7(30)
of Patients
Nonchemotherapy (N = 21) 10(48) 7(33)
Chemotherapy (N 17) 7(41) 6(35) =
Nonchemotherapy (N = 16) 6(38) 5(31)
_>18 mo_2( 9)_5(13)_2(11)_5(24)_2(12)_4(25)_ >24 1( 4)
mo
"Functioning
at
Table
a
normal
or near
normal
5(13)
1( 5)
4.—Probability of Significance of
Factors
Factors
Total No. of Patients
Severe neurological deficitf Present Absent
Affecting
:65 yr
