MATERIALS AND METHOD

NERIUM OLEANDER (N.O.) EXTRACTS; DOSAGES

N.O. extracts were prepared as described in Example 1 in the U.S. patent 5,135,745.

N.O. extracts have been applied in various forms. N.O.I. ( Nerium Oleander for injection)(or NOI for short) is used as I.M. injection; N.O.O. ( Nerium Oleander for oral use) (or NOO for short) is given orally.

In the succeeding descriptions and on other pages of this site, if a patient is stated to be given NOI, this will mean by intramuscular injection, and if a patient is stated to be given NOO, this will mean orally.

The extracts have a specific gravity of 1.012 g/cm3 (+/- 0.002g/cm3).

The therapeutic maximum dose of N.O. has been 1 cc/day (about 12 mg solid N.O. plant material/day) for NOI, and 3 cc/day
( about 36 mg solid N.O. material/day ) for NOO, both for a 60 kg person. In other words, the therapeutic maximum dose of NOI has been daily 0.017 cc/kg. day, or 0.2mg solid N.O. plant material/kg.

LD50 dose of NOI on mature Balb/c mice (20+/- 3 grams) was determined as 0.8cc/mouse (40cc/kg or 480 mg solid N.O. plant material/kg).

ETHICAL BASIS

The Medical Deontology Regulation (#11) of the Republic of Turkey states the following: "No human is to be performed a surgery, or to be applied a chemical, physical, or biological treatment if the purpose of the application is experimental. A treatment method may be applied if the orthodox treatment methods are concluded to provide no benefit for the patient after clinical or laboratory examinations, and if enough experimentation has already been performed on animals and good effect of the treatment were observed on such research. In order for the treatment to be applied to the patient, there should be high enough probability that the condition of the patient would ameliorate, and that the condition of the patient would not worsen as compared to the case in which he might have received a classical treatment. Though not practiced before, a new method may be applied if the survival of the patient could be accomplished."

The patients could receive N.O. treatment thanks to this clause of the Medical Deontology Regulation.

SCREENING OF PATIENTS

The following steps have been taken whenever a patient with an inoperable and advanced malignant disease presented to Dr. Ozel:

  • A TEST was performed in order to adjust the dosage. In about 70% of patients NOI caused an easily controllable fever. If the patient had a rise in body temperature after NOI injections, then the regimen would be a dosage such that the maximum temperature would be between 37.5-38.2o C. If no fever occurs after NOI injections, then a flat dose is recommended.

  • REGULAR treatment: Daily injections were given 6 days per week. In about two months following the start of N.O. treatment, the patient should undergo a check-up, and the findings should be compared to the baseline check-up. If the patient benefited from the N.O. treatment, a regression or at least a stand still of the disease should be shown in the follow-up. In such a case the patient would be recommended to continue the N.O. treatment in the regular manner. If follow-up examination after the first two months showed progression of the disease, this would mean that the N.O. treatment would not provide any benefit for that patient, and would not be recommended any further.

    In cases that NOI caused no fever from the beginning, then regular treatment scheme would be changed to maintenance when follow up check ups documented complete regression. Regular treatment period ranged, in general, from three to eighteen months.

  • MAINTENANCE treatment: Regular treatment was followed by a maintenance treatment that aimed to prevent relapse, if any. During this period the patient received one course of therapeutic dose of NOI at various time intervals that varied from 2 days to two weeks. If ever any fever or relapse occurred during maintenance, the scheme would be changed to regular. As a rule of thumb, the duration of the maintenance treatment may be stated to be equal to the duration of the regular treatment.

 

SIDE EFFECTS

When therapeutic dose of N.O. extracts were administered to patients with malignant diseases, the following side effects have been noted to occur:


Following NOI administration


  • In about 70% of patients NOI caused an easily controllable rise in body temperature. The fever caused by NOI starts normally in two-four hours following the injection, continues for two-four hours, and drops to normal range. If needed, an Aspirin or another analgesic may be used to drop the fever. This fever in cancer patients after NOI injections, does not occur anymore when all malignant cells disappear.
  • No nervous system complications were encountered.
  • No visual trouble has been recorded.
  • Effect on the urinary system: An increase in micturition was observed.
  • Allergic reactions: Seldom, itching and exfoliation of the epidermis were observed. If ever this occurred, most of the time adjuvant therapy with antihistaminics provided relief. If adjuvant therapy did not help, N.O. treatment was discontinued.
  • A local anesthetic was applied as an adjuvant if injection site felt painful.
  • Some patients experienced pain in tumors for a short time following NOI injections. If the pain was sharp, the administration of an analgesic as an adjuvant decreased the pain. If such a pain occurred it helped to reveal, sometimes, the location of some previously undetected tumors. This kind of pain experience usually disappeared within three weeks after the beginning of N.O. treatment.
  • Pain in breast glands, similar to that occurring during adolescence, has been noted in most cases. An increase in libido and sexual potency accompanied this symptom.
  • During regular treatment period, the leukocyte count was observed to rise above normal values, sometimes up to 12,000 - 18,000 range.
  • When some patients with anemic symptoms developed tachycardia, cardiotonic drugs were given as an adjuvant.
  • If NOI was going to cause a rise in body temperature, the patient might experience a shivering before the temperature started to increase.

 

Following NOO administration


  • NOO caused no rise in fever. NOO was recommended as an adjuvant to NOI in gastrointestinal system malignancies.
  • Gastrointestinal system: Nausea, vomiting, or diarrhea have been observed, seldom, in some cases when the patient was given NOO for the first time. Those troubles disappeared when a symptomatic therapy was applied as an adjuvant for a few days.

 

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