INSULIN AND CANCER CHEMOTHERAPY

Steven C. SGA, M.D., Clinical Instructor, Department of Family Medicine, University of Health Sciences/The Chicago Medical School

Unpublished article, 1987. Figures and 26 references [omitted here]. [We believe this paper was distributed by Dr. SGA publicly at a cancer conference.]

[ Summary by Chris Duffield. The original article may be available directly from Dr. SGA. ]

Insulin, in the insulin potentiation (IPT) protocol, can produce higher concentrations of anticancer drugs within cells, by enhancing cell membrane permeability or by acting on insulin receptors. The drugs can be given in lower doses, thus avoiding toxic side effects. Insulin can also stimulate DNA and RNA synthesis within cancer cells, and stimulate the cells into active cell cycle stages in which they are most sensitive to many anticancer drugs.

Breast, colon, and melanoma cancer cell types are known to have higher than normal densities of insulin receptors, making them better targets for these two effects. This could apply as well to other, and perhaps all, cancer cell types, as implied by the known secretion of insulin and/or substances cross-reactive with insulin by breast, lung, cervix, kidney, fibrosarcoma, and Hodgkin’s lymphoma cells, apparently as part of the system by which tumors acquire glucose resources at the expense of the rest of the body. Thus IPT uses the cancer cell’s own support mechanisms against it.

More research, both in basic sciences and in the clinic is needed to elucidate further the mechanisms working during the practice of IPT, and to corroborate the reported successes of this method.

[End of summary. References are included in the Bibliography page.]

[Four case reports are presented, courtesy of Donato Perez Garcia y Bellon MD and Donato Perez Garcia MD 3, as anecdotes to stimulate discussion and study. These cases, included in here in full, are also presented elsewhere on IPTQ.org.]

CASE #1: INFILTRATING ADENOCARCINOMA OF THE BREAST

This is the case of a 53 year old Hispanic female who first presented with a right breast mass in May of 1985. A mammogram (5/23/85 -fig.1) was suspicious for malignancy, and an excision biopsy of the lesion done on 6/1/85 reported an infiltrating ductal carcinoma of the right breast (fig.2). At that time, the patient underwent only 3 radiation treatments and thereafter failed to return. She next sought medical attention for her disease in August of 1986. Here, she presented with complaints of pain and swelling in her right breast with foul smelling discharge, pain with swelling and immobility in her right arm, frequent low-grade fevers (38.5 C) and a weight loss of 30 lbs (14 kg) in the last 2 months. On physical examination the patient appeared pale and weak. She was conscious and oriented, and in moderate distress with pain in her right breast and arm. Blood pressure 170/110 mmHg. Pulse 80/min and regular. Temperature 37.6∞ C. Respirations 16/min. Height 5f t. 4in. (1.62 m). Weight 165 lbs (73.4 kg). Head and Neck: Poor oral hygiene with multiple dental caries and missing molars. Tender cervical lymphadenopathy, bilateral; 2 x 1 cm lesions on the right, 3 x 1 cm lesions on the left. Chest: There is a single 3 cm tender lymph node in right supraclavicular fossa. Lungs clear. Heart sounds normal. Cardiac rate and rhythm normal. Breasts: The right breast is extensively involved with a neoplastic/inflammatory process, principally in its upper outer quadrant. This mass measures approximately 6-8 cm in diameter and is contiguous with a tumor mass involving the right axilla. The mass is firm, tender and adherent to underlying fascia. There is redness of the overlying skin, with ulceration in the right areolar area, productive of a foul-smelling, whitish discharge. There is a 4 cm firm, tender mass palpable in the left axilla. The left breast is normal. Abdomen: Normal, without masses, tenderness or organomegaly. Pelvic exam: Normal.   Extremities: There is evidence of obstruction to venous/lymphatic outflow of the right upper extremity as a result of the right axillary involvement. The right arm is swollen in its whole extent, and has a dark, reddish-brown discoloration. The arm is held in extension and abduction with a very limited range of motion from that position. There is 2+ bilateral pitting edema of the ankles. Nervous system: Grossly normal. Laboratory investigations: Hgb 12.0 gm%. Hct 39%. RBC 3.2 x 10^6/mm3. WBC 12,300/mm3 with a normal differential count. Glucose 70 mg%. Sodium 134 meq/l. Potassium 4.2 meq/l. Chloride 98 meq/l. BUN 20 mg%. Creatinine 1.1 mg%. Calcium 8 mg%. Phosphorous 3.9 mg%. Cholesterol 200mg%. Total protein 5.8 gm%. Albumin 3.2 gm%. Globulin 2.4 gm%. Bilirubin total 0.4 mg%. SGOT 38 mU/l. LDH 140 mU/l. Alk phos 50 mU/l. Urinalysis showed a trace of protein and 10-15 WBC/HPF. The patient refused other investigations ordered (chest xray, bone and liver-spleen scans). Her disease was certainly Stage III and very possibly Stage IV (T4 N3 M0_1?).

On August 19, 1986, the patient began a series of weekly treatments with insulin potentiation therapy. (The IPT protocol has a standard format within which different combinations of medications are given orally, intramuscularly and intravenously. Different medications are given according to the differing needs of individual clinical situations. The therapeutic rationale for using the various medications given in these treatments is generally consistent with the indications in standard pharmacology. Sometimes it is not. In these latter circumstances, it is the clinical experience of the treating physician that determines the drugs of choice. Another factor here is that the Mexican pharmacopoeia differs from that in the United States or Canada. The procedures in common to all applications of the IPT protocol will be given for this case only, and not repeated for each of the following cases. Only the medications given will be listed in these others.)

On the first treatment day, the patient arrived at the hospital in a fasting state, having taken a cathartic preparation the night before (X-Prep). She was given an enema consisting of 200 gm of Lactulose dissolved in 1000cc of tap water, and an intramuscular injection of Neostigmmne 5mg to promote a good evacuation of the enema. An IV was then started and run at a ‘keep vein open’ rate with lactated Ringer’s solution. She was then given an intravenous injection of regular insulin. After a 20 minute period of close observation, the patient was given her oral medications, taken with sips of water. The intramuscular medications were next injected into the upper outer quadrant of the buttock, one at a time. Finally the prescribed intravenous medications were administered, together with a quantity of 50% hypertonic glucose. The patient was observed for 6 hours following the giving of her medications. During this time, she received Soo cc of lactated Ringer’s solution IV, and was permitted tea or fruit juices ad libitum. The patient was then discharged from the hospital, advised to remain fasting for the rest of the treatment day and told that full alimentation could begin on the day following the treatment. This patient received the following medications in her treatments: regular insulin 4 units IV. Oral: Benexol-B12 (Roche) (B1 250mg, B2 250mg, B12 1mg) 1 tablet; Cholipin (Boeringer Ingelheim) (1,phenyl-1-hydroxy-n-pentane 100mg, dimethyl-n-octyl-(ethyl ester of beta-benzilic acid) ammonium bromide 100 mg) 1 tablet; Doryl (Merck) (carbamylcholine chloride 2mg) 1 tablet; Digenor (Rudefsa) (metoclopramide hydrochloride 10mg, dimeticone 40mg) 1 capsule; Daflon (Sanfer) (hesperidin 150mg, “diosmina” 150mg) 1 tablet; Foselite (Siegfried) (sodium alpha-oxybenzilphosphmnate 100mg) 1 tablet; ascorbic acid 150mg) 1 tablet; Lasix (Hoechst) (furosemmde 40mg) 1 tablet; Nolvadex (ICI) (tamoxif en 10mg) 1 tablet; Intramuscular: Iridus (Roussel) (“naftidrofurilo” acid oxalate) 2.4mg; Extracto Higado (Lilly) (liver extract) 0.5cc; Dotirol (Winthrop) (ampicillmn sodium 5OOmg/2cc) 0.5cc;

Genoxal (Schering) (cyclophosphamide SOOmg/25cc) 0.5cc; Methotrexate (Lederle) (methotrexate 50mg/20cc) 0.5cc; Intravenous: Cevalin (Lilly) (ascorbic acid 100mg/cc) 0.2cc; Calcium (Sandoz) (calcium gluconate 1.375gm/lOcc) 2cc; Alin (Chmnomn) (dexamethasone sodium phosphate 4mg/cc) 0.4cc; Fluoro-uracil (Roche) (5-fluorouracil 200mg/lOcc) 0.2cc; Anistal (Silanes) (ranitidmne hydrochloride SOmg/Scc) 1cc; Garamacina (Scheramex) (gentamycin sulfate 40mg/cc) 0.5cc; Keflin (Lilly) (cephalothin sodium lgm/5cc) 0.5cc; Carbecin (Sanfer) (carbenicillin disodium lgm/2cc) 0.5cc; 50% hypertonic glucose solution 50cc.

During the patient’s course of treatment, she experienced no adverse reactions from the chemotherapeutic agents used, nor from the insulin injections. A control mammogram was done on October 28, 1986, following the patient’s 10th treatment. This reported “. .a slight thickening in the skin in the right retroareolar area. Actually no calcifications or tumor masses are identified. It is considered that there exists a notable improvement and/or cure.” Clinically, the patient was well. There was some thickening of the skin in the right breast, but there were no palpable masses in either breast. The cervical, supraclavicular and axillary lymphadenopathy were likewise no longer palpable. The patient’s * right arm had returned to its normal size and color, and was fully functional. The patient continues with follow-up and, to date (5/87), has shown no evidence of recurrence of her disease.

CASE #2: ADENOCARCINOMA OF THE LUNG

This is the case of a 45 year old non-smoking female who presented with a left Horner’s syndrome. In September, 1985, a chest xray demonstrated an infiltrate in the left lower lobe (fig.4), and a percutaneous needle biopsy reported a large cell adenocarcinoma of the lung. This diagnosis was confirmed by bronchoscopy with fine needle aspiration (fig.5). The patient began treatment with IPT on November 12, 1985. At this time, the patient complained of a non-productive cough and a persistent pain over her left hemithorax. On physical examination, the blood pressure was 98/60. Pulse 108/min and regular. Temperature 36.70 C. Weight 140 lbs (62 kg). Positive physical findings were restricted to examination of the patient’s left eye and her chest. The patient had anisocoria with miosis of the left pupil and ptosis of the left upper eyelid, all consistent with a left Horner’s syndrome. Anhidrosis was not present. In the chest, the respiratory excursions were full and there was no dyspnea. The breath sounds were decreased over the left hemithorax posteriorly and laterally, and minimal crepitations were heard here. No egophony was appreciated. In the extremities there was no clubbing, cyanosis or edema. Laboratory investigation: Hgb 14.0 gm%. Hct 43%. RBC 4.26 x 10^6/mm3. WBC 13,500/mm3. Total protein 6.3 gm%. Cholesterol 229 mg%. bilirubin total .71 mg%. Alk phos 43 mU/l. GGTP 8mU/l. The xray examinations of the chest have been described. With the Horner’s syndrome, the patient’s disease was classified as Stage III (T3 N0 M1).

In her weekly IPT treatments, this patient received the following medications: Insulin 5 units IV. Oral: Benexol-B12 (Roche) (B1 250mg, B2 250mg, B12 1mg) 1 tablet; Cholipin (Boeringer Ingelheim) 1 tablet; Digenor (Rudefsa) 1 tablet; Zaditen (Sandoz) (“ketotifino” 1mg) 1 tablet; Zyloprim (Welcome) (allopurinol 300mg) 1 tablet; Lasix (Hoechst) (furosemide 40mg) 1 tablet; Myambutol (Lederle) (ethambutol 200mg) 1 tablet; Intramuscular: Iridus (Roussel) 1 tablet; Extracto Higado (Lilly) 0.5cc; Estreptomycina-S (Lakeside) (streptomycmn sulfate 500 mg/cc) 0.5cc; Genoxal (Scheming) (cyclophosphamide SOOmg/25cc) 0.5cc; Methotrexate (Lederle) (methotrexate SOmg/2Occ) 0.5cc; Alupent (Boeringer) (orciprenalmne sulfate 0.5mg/cc) 0.2cc; Depomedmol (Upjohn) (methylprednisolone acetate 20mg/cc) 0.4cc; Hemosin-K (Hormona) (vitamin K 10mg, adrenochromo-monosemicarbazone 10mg/5cc) 2cc; Gadital Yodico (Italmex) (iodine .1mg, eucalyptol 100mg, guayacol 100mg, menthol 50mg, vit A 4000iu, vit E 100iu/5cc) 5cc; Intravenous: Cevalin (Lilly) 2cc; Calcium (Sandoz) 2cc; Manibee-C (Endo) (B-complex solution 10cc) 0.5cc; Alin (Chmnomn) 0.2cc; Anistal (Silanes) 1cc; Cambenicin (Sanfer) (carbenicillmn disodium lgm/2cc) 0.5cc; Garamicina (Scheramex) 0.5cc; Keflin (Lilly) 0.5cc; 50% hypertonic glucose 20 cc. The patient experienced no untoward side-effects of her treatments, and after the 8th one a control chest x-ray was done (March 4, 1986). It showed a significant reduction in the left lower lobe lesion with a disappearance of the satellite lesions (fmg.6). Clinically, her cough and back pain were gone, while the Horner’s syndrome remained unchanged. Except for the persistence of this, the patient continues under treatment in a good-state of health, free of symptoms either from her disease or from the treating medications. This patient’s latest follow-up chest x-ray (? Date/1987) shows almost complete clearing of the lesion in her left lower lobe (fig.7).

CASE #3: CARCINOMA OF THE CERVIX

This is the case of a 22 year old female who presented in February of 1970 with lower abdominal pain, dysuria, leukorrhea and occasional intermenstrual bleeding. The patient was G2 P2 A0 and her last pregnancy ended in September, 1969, with a normal vaginal delivery. She was found to have a mass in the vagina, and a biopsy of this (March 5, 1970) described the lesion as a “carcinoma of the cervix, mixed adenoacanthoma Grade II, with adaptive stroma”. The patient presented for her first IPT treatment on March 18, 1970. At this time, in addition to the above symptoms, she also complained of dysuria, tenesmus and a weight loss of 18 lbs (8 kg) over the last month. Physical examination revealed a 22 year old female looking somewhat older than her stated age. She was in moderate distress with her lower abdominal and perineal pain. Blood pressure 172/78. Pulse 80/min and regular. Temperature 36.5∞ C. Height 5’6″ (1.69 m). Weight 117 lbs (52 kg). The positive physical findings are restricted to the examination of the abdomen and pelvis. The abdomen is flat and moderately rigid with some guarding in the lower abdomen. There are no masses or organomegaly palpable. The bowel sounds are normoactive. There is diffuse tenderness in the lower abdomen. Pelvic examination revealed a normal appearing introitus except for the blood stained, fetid vaginal discharge. The visualized cervix was large and irregularly deformeff with bleeding ulcerations. The mass of it measured approximately 6 cm in its greatest dimension. Bimanual examination showed the cervical lesion to be hard and painful to the touch. The uterine fundus was retroverted and not palpable. There were no adnexal masses. Rectal exam disclosed a hard, tender, irregular mass palpable through the anterior rectal wall. There was no evidence of direct extension into the rectal wall itself. This patient refused any investigations that would have allowed for an appropriate staging of her disease. As best as could be determined clinically, she had a Stage Ila or lIb disease. The patient received 9 IPT treatments with the following medications: Insulin 20 units IV. Oral: Chloromycetmn (Parke Davis) (chloramphenicol 500mg) 1 tablet; Lasix (Hoechst) 1 tablet; Triurol (AF) (nalidixmc acid 500mg) 1 tablet; Quimar oral (Grossman) (trypsmn and chymotrypsin 100,000 units) 1 tablet; nicotinic acid 50mg; Intramuscular: Endoxan (Asta Werke) (cyclophosphamide 100mg/cc) 1cc; madribon (sodium sulfanilamide Soomg/5cc) 0.5cc; Synkavit (Roche) (menadione 10mg/cc) 2cc; Decadron (Merck) (dexamethasone 4mg/cc) 0.5cc; Betalin Complejo (B complex solution) 3cc; Imferon (Lakeside) (iron dextran = 50mg iron/cc) 2cc; Intravenous: Acriflavin hydrochloride 20mg; methylene blue 1mg; resorcinol 1mg; tetracycline 125 mg; hexamethylenetetraammne 0.5 mg; 50% hypertonic glucose solution SO cc. After the patient’s 9th and last treatment, a Pap test was done and reported as negative. Another biopsy was also done and the report of this read: “Chronic cervicitis with leukoparakeratosis and foci of squamous metaplasia. No signs of anaplasia are observed”. Clinically, the patient’s morbid condition was seen to have resolved completely. She has survived in a disease-free state for almost 16 years, and has since completed another pregnancy, delivering vaginally.

CASE #4: EWING’S SARCOMA OF THE BONE.

This is the case of a 3 year old female who had suffered an apparent fracture of her left wrist in June of 1970. When the cast was removed, the swelling and pain persisted. A repeat x-ray showed gross deformity of the distal radius on the left (fig.8), and a subsequent biopsy reported the lesion to be a Ewing’s tumor of the bone. A skeletal survey showed that metastatic lesions were already present in other bones. The parents were apprised of the grave prognosis in the case, and told that there was no effective treatment for the advanced stage of the child’s disease. The parents brought the child for a trial of IPT treatments, the first one being given on August 18, 1970. Physical examination at that time revealed a 3 year old female in some slight distress with pain and swelling in her left wrist. She had a history of frequent febrile episodes and a recent weight loss of 9 lbs (4 kg). Blood pressure 80/40. Pulse 90/min and regular. Temperature 37∞ C. Height 3′ 7″ (1.06 m). Weight 40 lbs (18 kg). Head and Neck; There is bilateral cervical and supraclavicular lymphadenopathy, tender, averaging 1-2 cm in size. HEENT otherwise normal. Chest: Heart sounds normal. No murmurs. Lungs clear. Abdomen: Soft without masses, tenderness or organomegaly. Nervous system: Grossly normal. Extremities: The distal left forearm is swollen and has a noticeable varus deformity. The area is exquisitely tender. There are also three 1 cm epitrochlear nodes on the left elbow.

The child received a total of 17 treatments for her disease. These were tolerated without incident or drug-related side-effect. The medications given in these treatments were as follows: Insulin 5 units IN. Oral: nicotinic acid 100mg 1 tablet; Intramuscular: Madribon (Roche) (sodium sulfanilamide 500mg/5cc) 0.3cc; Roniacol (Roche) (beta-pyridyl-carbinol) 0.3cc; Manibee Complejo (Dupont) (vitamin B-complex solution) 0.3cc; Lasix (Hoechst) (furosemide 20mg/cc) 0.3cc; Endoxan (Asta-Werke) (cyclophosphammde 100mg/cc) 0.3cc; Intravenous:methylene blue 0.2mg; resorcmnol 0.1cc; hexamethylenetetraamine 0.5mg; Italcalcio Vitammnico (Italmex) 2cc; magnesmum bromide 25mg/cc 1cc.

In the middle of her course of treatment, an x-ray was taken of the left wrist (fig.9) and demonstrated good bone neoformation with reestablishment of a more normal contour to the distal radius. Upon completion of the series of treatments, the child was clinically well in all respects. She survives in good health to the present. Figure 10 shows the condition of the left wrist bones in this patient 8 years post treatment.

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