Download 1 Oncothermia as monotherapy A.Szasz Spontaneous tumor

Oncothermia as monotherapy
A.Szasz
Dept. Biotechnics, St.Istvan University, Hungary
Spontaneous tumor regression (or even curing) by heat/fever effects believed by many
patients and it is under intensive debate for a long time in the professional literature
also. As early as in the beginning of the last century 185 spontaneous regressions were
collected [1] and also collection of cases were published in early 1960’s: 202 cases
were collected within 4 years [2], while 98 cases shown also in the middle of that
decade [3]. Many surprising spontaneous remission were described in a monograph [4].
Few years ago the famous “Armstrong effect” [5], had been in focus of the topic. The
literature of the spontaneous remission of cancer is impressive, and all of them
somehow connected to the fever or heat [6], [7], [8], [9]. Large number of clinical cases
are collected for study the topic: 176 cases between 1900–1960, [10], [11]; 489 cases
described from 1900–1987 [12]; and a large meta-analysis was applied for about 1000
cases [13].
In fact the classical hyperthermia as monotherapy was applied in many studies at the
historical time of hyperthermia. In ancient applications, no other treatment facilities were
available, [14]. Hyperthermia alone is a popular (almost unique) application for in-vivo
experiments like [15]. In former times many human clinical trials were performed as
monotherapy applications [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27],
[28], [29], [30], [31], [32], [33], [34]. At the design of the clinical trials in hyperthermic
oncology it was counted as an option, but the results of the combined therapies was
found better [35].
In an extended study the localized hyperthermia alone has been used for the treatment
of cancer in cases of recurrences in which previously administered conventional
therapies have failed [36]. 57 patients with 60 lesions have been treated by microwave
and radiofrequency methods, twice a week, 6-8 times. Complete response (CR) was
obtained in ten cases (16.6%) and partial response (PR) in 14 (23.4%). Higher rates of
CR were observed in the chest wall (38.5%) compared with the head and neck area
(11.4%), trunk (l0%), and limbs (none). Adenocarcinoma was the most responsive
histologic type (40%). Squamous cells carcinoma had 7.7% CR. The only case of
undifferentiated carcinoma showed CR; there were none on five sarcomas. Long-term
local control (24 months) was approximately 7%.
Oncothermia is typical complementary treatment for GS methods, first of all for radioand chemotherapy but growing number in pre- and postoperative applications as well.
We have to strictly emphasize: while the GS therapies could be applied with the chance
of success, oncothermia could be only complementary for these, sensitizing, boosting
their effects and reducing their (sometimes severe) side effects.
1
However, oncothermia was provided many times as monotherapy in the cases when no
other “gold standard” (GS) treatments facility is applicable. Some of the cases are
blocking the complementary applications (organ [like liver, kidney] failure, low blood
count, severe side effects of GSs, psycho-rejection, very low immune status, definite
refractory cases etc.). In such situation oncothermia could be applied as monotherapy.
It has consequences:
1. In this meaning oncothermia is palliative from the point of view of GS. Effect of
this palliation could be immediately observed on the quality of life and measured
by Karnofski Performance Score (KPS).
2. The obtained results in palliative approach of oncothermia are many times
curative in these cases as well. It could even resensitize by oncothermia the
anyway refractory GS, and so they could be reapplied complementary again.
3. Patients treated by oncothermia all are in advanced stages, many times terminal.
4. Evidence based statistics are not available when GS is failed, the cases are very
individual, patients have frequently co-morbidities, low immune status, low KPS
and almost all individuals are psychologically frustrated. Oncothermia for them is
a “last hope” treatment.
2
Some cases can be cited for monotherapy:
Esophagus carcinoma.
Department: Department of Radiology and Microtherapy, University of WittenHerdecke, Bochum, Germany. Investigators: Prof.D.Gronemeyer & Dr.H.Sahinbas.
Patient: M, 46 y, male, Diagnosis: 4/00, Esophagus-Ca.
Therapies:
1. Surgery: 4/2000.
2. Chemotherapy: Multiple CxT,
3. Radiotherapy: (50 Gy) from 01.08.2001,
Result 1: recidiv. Anastomiosen recidiv / Multiple bougienage and Anastomose, Full
block of food-passage, low KPS
Oncothermia: monotherapy from 27.09.2001 –23.11.2001
Result 2: Complete remission (CR) Free-food passage
01.08.01.
29.11.2001
after 6x oncothermia
17.01.2002
after 12x oncothermia
3
Liver metastasis from sigma carcinoma primary
Department: Department of Radiology and Microtherapy, University of WittenHerdecke, Bochum, Germany. Investigators: Prof.D.Gronemeyer & Dr.H.Sahinbas
Patient: A.K, 61 y, male; Diagnosis: 11/97, Sigma-Ca. Tumor-classification: pT3 N1
M0; Size: 4 x 5 cm, Metastasis: hepatic; Therapy (for metastasis): Oncothermia
alone (no chemotherapy or other was available) Result: Partial remission (PR) tumor
and tumor marker regression


4
Astrocytoma, WHO III.
Institute: HTT-Med Polyclinicum, Budapest, Hungary, Investigator: Dr. A.Varkonyi,
June 1998,
after 2nd session
of oncothermia
June 1997,
before oncothermia
Patient: P.I. 45 y, female; Diagnosis: Anaplastic astrocytoma; Stage: WHO III;
Treatment: Oncothermia monoterapy from June 1997 Result: Complete remission
(CR)
5
Astrocytoma, WHO III.
Institute: Biomed Clinic, Bad Bergzabern, Germany. Investigator: Dr. Dr. D. Hager
Patient: K.D. male, Diagnosis: Anaplastic astrocytoma, Stage: WHO III
Treatments: Surgery: Sept./2000 Excision of tumor, Radi ation: Sept.-Nov. 2000
postoperative radiation. Chemotherapy: Sept.2000-Jan.2001 (BCNU+VM-26).
Recurrence: Febr.2001 (4x1.5 cm).
Oncothermia: Febr. 2001 with Thal. & bosw. s. Result: Complete Remission (CR)
6
Astrocytoma, WHO II.
Institute: Institute of Microtherapy, University Witten Herdecke, Germany.
Investigators: Prof.Dr.D.Gronemeyer & Dr.H.Sahinbas
Patient: W. B. 49y, Female. Diagnosis: Astrocytoma WHO II.
Treatments:
Surgery:
1. January 1999
2. October 1999
Radiation:
1. Nov.-Dec.1999 60 Gy
2. July 2001
30 Gy
Chemotherapy: July 2001;
12 Cycles Temozolomide;
Result 1: recurrence July 2002
Oncothermia: monotherapy. 10 July.-24.July, 2002. 8 x sessions, 60 min
Result 2: Histologicly tumor-free, only necrotic tissue
Before oncothermia
After oncothermia
(monotherapy)
Only necrotic tissue
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Astrocytoma, WHO III.
Institute: Biomed Clinic, Bad Bergzabern, Germany. Investigator: Dr. Dr. D. Hager
Patient: F.M. male. Diagnosis: Anaplastic astrocytoma, Stage: WHO III
Treatments:
Surgery:
1. Jun.2001 Subtotal resection
2. Aug.2001 Relapse, subtotal resection again
Radiation:
Sept.-Oct. 2001 postoperative radiation (TD 60 Gy)
Chemotherapy:
Jan.2002-Jun.2002, Temodal (7cycles)
Result 1: Progressive disease (PD)
Oncothermia: Since. Jun.2002 with Thal. & bosw. s. & ELP
Result 2:
Complete Remission (CR)
MRI 21.06.2002
MRI 11.06.2004
MRI 21.06.2002
8
Astrocytoma, WHO III.
Institute: Biomed Clinic, Bad Bergzabern, Germany, Investigator: Dr.Dr. D.Hager
Patient: C.C. male. Diagnosis: 09/93 Anaplastic astrocytoma, Stage: AAC WHO II,
Inoperable.
Treatments: Radiation: 10-12/93 (TD 54 Gy). Result: Recurrence 07/94; AAC WHO III
Chemotherapy: 08/94 – 07/95 (5xPCV). Result: Progression, 01/96, (MRI)
Oncothermia, (monotherapy) Since 01/96
Results: 1. Central necrosis with perifocal edema, decrease in vascularization 12/96;
MRI. 2. Partial Remission; 12/97. 3. No change (NC); MRI, since 11/98. 4. Follow
up: till 06/04 (MRI)
9
Pediatric ependymoma, WHO III
Institution: Institute of Microtherapy, University Witten Herdecke, Germany
Investigator: Prof. Dr. D. Gronemeyer & Dr. H. Sahinbas,
Patient K.K. 10 y, (boy), Diagnosis: progressive ependymoma, bithalamic. Stage:
WHO III, Treatments: conventional: 1st surgery, 2nd chemotherapy, 3rd radiotherapy
and chemotherapy. Failed all, Karnowfsky score down to 30%.
Oncothermia (since 09.Dec.2003) (monotherapy), 60 min, 2-3 times weekly,
21.04.2004 after
1st session of
oncothermia
17.11.03.
before oncothermia
17.11.03.
before oncothermia
21.04.2004 after
1st session of
oncothermia
Karnowski Index [% ]
Karnofsky Score
80
70
60
50
40
30
20
10
date
0
December 2003
January 2004
March 2004
May 2004
10
Intrahepatic bile-duct carcinoma
Institution: Markusovsky Hospital, Szombathely, Hungary. Investigator: Dr. A.Csejtey
& Mr.P.Lorentz.
Diagnosis: Intrahepatic bile-duct carcinoma, inoperable. Therapy: Oncothermia as
monotherapy with concomitant supportive vitamins only. Prognosis: overall median
survival 6 months. Due to the patient’s status, no any other therapies was possible.
Oncothermia started (June14.2007)
Tumor-progression (May 08.2007)
Definite tumor-regression (December 19, 2007)
11
Clinical study for liver metastasis from colorectal cancer primary [37] (n=80)
Institute: Biomed Clinic, Bad Bergzabern, Germany. Investigator: Dr.D.Hager
Histology: Adeno-carcinoma, Prior liver resection: 16%, All patients had metastases.
Median survival [months]
number of patients
30
25
24.4
20
15
10
21.5
24.1
80
80
80
60
50
11
30
Oncothermia Oncothermia +
alone
chemotherapy
after failure of
(various)
prior treatments
40
20
5
0
100
All
therapies
Expected
survival
(historical)
0
patient number
median survival [months]
Prior chemotherapy unsuccessful, 37.5% of patients had palliative chemotherapy
concomitantly with oncothermia, others had monotherapy. Oncothermia alone was more
successful than with concomitant chemotherapy. The reason is probable the low
immune status of the patients with advanced diseases, and the intolerable side effects.
12
Advanced hepatocellular carcinoma (HCC) phase II study [38] (n=22)
Institute: Department of Oncology, Spedali Civili, Brescia, Italy. Investigator:
Prof.VD.Ferrari.
Patient characteristics: Number of patients: 22. Stage C (of BCLC classification). Nonoperable: 68%. Portal vein-thrombosis: 70%. Distant metastasis: 9%.
Oncothermia treatment: 60 min/session, 2 sessions/week. 10 sessions/cycle, Median
1.5 cycle (1-4), 80-140 W (41-47oC)
Local clinical response
80
Quality of life: better 50%
70
72
60
50
40
30
23
20
5
10
0
0
CR
PR
NC
Concomitant chemotherapy
Toxicity
80
70
PD
70
68
64
60
60
50
50
36
40
40
30
30
18
20
14
10
20
10
0
0
Not observable
Erithema
Subcutan adipose
burn
Concomitant oxalyplatine
(50 mg)
No concomitant chemotherapy
13
Far-advanced liver metastases (various primary tumors) [39]
Institute: Clinic & Institute of Radio-Oncology, Zentralkrankenhaus Reinkenheide,
Bremerhaven, Germany. Investigator: Prof.H.Aydin
Topic: Far advanced liver metastases various kind of primer tumors. Concomitant
therapies were applied whom it was possible. Oncothermia: 2x / week.
Concomitant chemotherapy: Vinorelbine (20 mg/m2/week)
Concomitant radiotherapy: 10MV, 1.5-1.8 Gy fractional radiation 5x /week, overal
dose: 21-24 Gy.
Protocols:
Therapy / week-days
Radiotherapy +
Oncothermia
Mon.
Tue.
Wed.
Thu.
Fri.
RT
RT
OT
RT
RT
OT
RT
Number
of
patients
16
CHT
Chemotherapy +
Oncothermia
OT
OT
8
Oncothermia monotherapy
OT
OT
4
Local control (overall response)
80
75%
Oncothermia + Radiotherapy
Oncothermia +Radiotherapy: 81%
70
Oncothermia + Chemotherapy
(Vinorelbine (20mg/m2/week)
Oncothermia + Chemotherapy: 38%
60
Oncothermia alone
62%
Oncothermia as monotherapy: 25%
50%
50
40
31%
30
25% 25%
19%
20
13%
10
0
0
0
CR
0
5/16 1/8
PR
0
8/16 2/8 1/4
SD
3/16 5/8 3/4
PD
The most advanced refractory cases were treated by monotherapy oncothermia alone.
Probable this is one of the factors of the result.
14
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