hope for patients with Brain Tumors is now emerging. Malignant Brain Tumors
(Gliomas-Astrocytomas) are rarely curable by Surgery and/or Radiotherapy alone. Chemotherapy, as generally available,
has been of very limited value.
form of intensive chermotherapy, commonly known as High
Dose Methotrexate with Citrovorum Factor Rescue was invented by Dr.
Djerassi in the 1960’s and was recently perfected by him as a most effective treatment for Brain Gliomas
(glioblastoma multiforme, anaplastic astrocytomas, oligodendroglioma and related
tumors). Dr. Djerassi has treated
over 200 patients with brain gliomas with this drug and method.
Gliomas are tumors, usually
malignant which are derived from the Glia cells of the brain or of the spinal
cord. The Glia cells act as the
connective tissue of the central nervous system.
The most common type of Glioma is the Astrocytoma. This tumor occurs in a variety of histologic types, pure or mixed, with a varying degree of aggressive malignancy. It is divided into four (4) Grades with Grades 3 and 4 consistently very highly malignant. Previously, Grade 4 Astrocytoma was called Glioblastoma Multiforme (in Latin). Recently Grade 3 and 4 both have been included in this term. The lower grades, 1 and 2, are jointly called Anaplastic Astrocytoma. They advance and progress slowly, on occasion over 10 years, with an average of 2 1/2 to 5 years. Eventually most anaplastic gliomas change towards the higher grades (Grades 3 or 4) and are, therefore, usually fatal. Astrocytomas, Grade 2 or 1, recurring after initial surgery and/or radiation, are invariably fatal.
High Dose Methotrexate with
Citrovorum Factor (Leucovorin) “Rescue” which proved CURATIVE for Leukemias, Lymphomas and Osteogenic
Sarcoma (bone cancer), was also most helpful to patients with Ovarian, Breast, Stomach (gastric) and Head and Neck Cancers in studies carried around the
world from the mid 60’s to the 90’s.
(References - See below).
the early 80’s the promise of High Dose Methotrexate for treating, and possibly
curing some types of Glioma-Astrocytoma was suggested by the dramatically
prolonged survival of a number of
patients treated with High Dose Methotrexate in the 60’s and 70’s.
Intensive studies to perfect
and adjust this treatment for use in Brain Tumors as well as to extend the
experience with it to Gliomas were carried out since then.
group of 87 patients with Brain Glioma - Astrocytoma, all very advanced
and failing every thing else were treated with High Dose Methotrexate usually in
doses higher than previously used and with improved Rescue (with
Leucovorin). The effect of this treatment on the size of the
cancers (by CT or MRI) was dramatic. Objective response (shrinkage) by CT scans was found in 70.9% of evaluable
patients. The symptoms
improved in the same proportion (70.7%). The results were most common (90%) in
the smaller tumors (less than 3cm) and in 50% of the massive tumors. The responses were seen in 6 of 11
patients with Grade 1 and 2, 24 of 30 with Grade 3 and in 22 of 33 patients with
Grade 4 disease. Six improving
patients of the remaining eight had unclear grade number. These results are summarized in the
study continued beyond the above experience with the same results until survival could be calculated in a group
of 197 patients. Those included 74 patients with Grade 4
Astrocytoma, 52 patients with Grade 3, 23 patients with Grade 2 and 6
patients with Grade 1. The Grade 2
and 1 were recurring with an accelerated form of the disease.
remaining (42) patients could not be evaluated for survival due to lack of
follow up or uncertain histology (grade).
10 patients (2 children) had a histology between Grade 2 and 3 with
rapidly progressing disease.
Eighteen of 57 patients (31%) with advanced and
terminal Grade 3 (including 4 with Grade 2 to 3 or 2 1/2) were alive and well at 10 to 28 years with a median
of over 10 years.
Four of the 18 long-term survivors received this chemotherapy
only, with no radiation therapy at all. Higher success rate is expected in
recently diagnosed and previously untreated patients in good general
concept and technology of this chemotherapy was developed by Dr. Isaac Djerassi,
first at the Childrens Hospital of Boston, jointly with Dr. Sidney Farber, the
inventor of Methotrexate, and then at the Childrens Hospital of Philadelphia
during the late 1960’s. This chemotherapy is widely used today for the cure of Acute
Leukemia, Non Hodgkins Lymphoma and Osteogenic Sarcoma. The superb results in Brain Tumors is
the latest advance with the treatment.
This chemotherapy employs
massive doses of a well known and widely used FDA approved drug -
Methotrexate. A precision use of a
special antidote (tetrahydrofolic acid = “citrovorum factor leucovorin”)
eliminates most of the side effects of this treatment, allowing the excess drug
to cross the blood brain-barriewr and attack the tumor.
For additional information, click
below on the following;
1. High Dose Methotrexate with Citrovorum
2. Djerassi, I., CV
clinical data, table and scientific publication about this work, continue
RESULTS WITH OTHER
Patients with other types of
cancer were studied extensively over 30 years by Dr. Djerassi and by others. Many were found very responsive to Dr.
Djerassi’s chemotherapy. The
results were published and are described in the references below. The publications by others are grouped
below by Institutions of origin.
* Lung Cancer - highest improvement
rate and largest survival.
* Ovarian Cancer - potentially
* Mesothelioma (asbestos cancer) -
best results and survival.
* Stomach (gastric) and Bladder
Cancers and Sarcomas - potentially curative when
used before and after surgery.
Effective also in recurring tumors.
* Breast Cancer - best improvement
and survival. Curative when used
after surgery as adjuvant.