Several Side Effects I Have Observed Clinically in Cancer Patients on PD-1
As early as two or three years ago, patients who had used PD-1 began reporting its side effects to me, and I myself have participated in diagnosing and managing some of the adverse effects seen in cancer patients on PD-1.
I hesitated for a long time about writing this article, because many posts on my public account do exert some influence on cancer patients. I worried that with insufficient data I might misjudge PD-1's side effects and that what I wrote could affect some patients' decisions about PD-1.
But over the past two years I have seen more and more patients who developed severe side effects after PD-1, and I feel I should write this article. I hope, through my own self-media platform, to collect more real-world clinical data from PD-1 users, further explore the effects and side effects of this new immunotherapy that cancer patients flock to, and search for ways to manage the series of adverse effects it causes.
I hold no bias against PD-1. Though I now focus on TCM research, as a former science and engineering student (with near-perfect scores in math, physics, and chemistry) I have no resistance to modern medicine. I hope to discuss PD-1 as objectively and fairly as possible, not with prejudice.
The number of cancer patients I have seen on PD-1 is limited—only forty or fifty—and since they came to me, most had either developed problems on PD-1 or failed to respond to it. So this is only a preliminary article. I hope readers who have truly used PD-1 can provide richer, more comprehensive data to help me build a complete picture.
I would rather not understand PD-1 by reading articles supplied by institutions promoting it. To be factual, those articles are too optimistic and conceal the fact that PD-1 can cause severe, even fatal, side effects in some patients. I cannot find real data from those institutions.
For some patients, PD-1's side effects are far greater than those of chemotherapy or TCM. Severe pulmonary infection, persistent fever, hyponatremia, unbearable pain, edema, and malignant effusion are the most serious side effects I have observed. Several patients died within a month of starting PD-1 because their adverse effects could not be controlled.
Moreover, there is an odd claim—reportedly from certain PD-1 promotion teams and physicians—that PD-1 cannot be used together with Chinese herbs, especially herbs like Huangqi (Astragalus) and Dangshen (Codonopsis). The organizations or individuals making this claim produce no clinical trial data at all; they define it by personal intuition, seriously misleading patients.
Without double-blind comparative data, without any research report, concluding this merely from the intuition of doctors who do not understand TCM obviously violates scientific spirit and medical ethics. I will give examples of how I used TCM to help patients with severe PD-1 side effects resolve them and even eliminate their cancer.
Some of these patients' data I have even submitted to our provincial Health and Family Planning Commission, which has verified the cases. If legitimate medical institutions or government bodies need my patients' data, I will cooperate and provide it for verification and research.
I can say responsibly that the claim that Chinese herbs—especially raw Huangqi—cannot be used with PD-1 is pure nonsense. Now many patients on PD-1 who develop severe side effects are left helpless by Western medicine, with nothing to do but wait for death. It is TCM, based on clinical medication experience, that can rescue some of them.
I hope this absurd claim—that Chinese herbs harm PD-1 patients—stops spreading. Such spreading only misleads patients and families; especially when a patient has severe side effects and is dying, this prejudice directly causes unnecessary death.
The most common PD-1 side effect is severe pulmonary infection. Lacking comprehensive data, I cannot calculate what proportion of PD-1 patients develop it, and many Western physicians at domestic institutions, when recommending PD-1 to patients, themselves lack understanding of these side effects.
A patient's family told me that the doctor at a certain Grade-A tertiary hospital who had recommended PD-1 to her family member understood the side effects even less than she did. This is factual. Because PD-1 is a new therapy not yet widely deployed domestically, sparse clinical data leave many doctors unaware of the adverse effects patients may develop.
After pulmonary infection, many patients not only have persistent fever but also develop pleural effusion. Because these side effects are underestimated, most doctors do not take them seriously, and some patients die of the syndrome following PD-1-induced pulmonary infection. I have personally seen at least three such cases.
PD-1 therapy, or PD-1 plus chemotherapy, can also cause hyponatremia, which is fairly intractable; in some patients sodium repletion fails. The resulting raised intracranial pressure causes severe drowsiness and listlessness, and in severe cases coma.
After PD-1 or PD-1 plus chemotherapy, some patients develop severe edema. I have seen multiple patients on PD-1 whose legs swelled until the skin was shiny and they could not wear shoes or walk at all.
PD-1 also causes severe pain in some patients. Two patients, after starting PD-1, could not endure severe pain and asked me for help. In both, I relieved the pain through TCM pattern differentiation and treatment.
Below is part of the case record for a patient surnamed Wang (a professor at a Lanzhou university). Because this patient followed me for a long time and the full record is very long, I excerpt only the PD-1 treatment phase.
Patient follow-up, May 15, 2017
After the previous follow-up, the patient was readmitted for radiotherapy and then received immunotherapy with Opdivo brought back from the U.S. Currently: liver metastasis, lung metastasis, bilateral kidney metastasis, soft-tissue metastasis in the right pulmonary phrenic recess, multiple lymph-node metastases, intracranial metastasis, spinal-cord metastasis, right pleural effusion. Albumin and total protein are low, coagulation time prolonged, lower bleeding. Pulse: fine and rapid; the chi-cun pulse is weak.
Recent foot swelling, nausea, no appetite, lower abdominal distension and pain. Cannot pass stool independently; needs Kaiselu (glycerin enema). After taking Guipi Wan (Spleen-Returning Pill), mouth ulcers and severe lower bleeding. Already paralyzed, in a wheelchair.
Currently taking Jinkui Shenqi Wan (Golden Cabinet Kidney-Qi Pill); foot swelling slightly improved.
Prescription: raw Huangqi (Astragalus) 30g, Han Fangji (Stephania) 30g, raw Baizhu (Atractylodes) 30g, Fuling (Poria) 30g, Zhuling (Polyporus) 30g, Huainiuxi (Achyranthes) 10g, Cheqiancao (Plantago) 15g, Mohanlian (Eclipta) 15g, Nüzhenzi (Ligustrum) 15g, Baiji (Bletilla) 10g, Chenpi (Aged Tangerine Peel) 10g, Fabanxia (processed Pinellia) 10g, Huoxiang (Patchouli) 10g, Peilan (Eupatorium) 10g, Xiaoji (Cirsium) 10g, Daji (Cirsium) 10g, Diyu (Sanguisorba) 10g, Jiao Sanxian (three fried stomachics) each 15g, Jineijin (Chicken Gizzard Lining) 30g, Pugongying (Dandelion) 30g, Jinyinhua (Honeysuckle) 30g (added later), Yejuhua (Wild Chrysanthemum) 10g, Tiankuizi 10g, Diding (Viola) 10g, Yiyiren (Coix) 60g, Xuanshen (Scrophularia) 15g, Zhebeimu (Fritillaria) 15g, raw Muli (Oyster Shell) 30g (decocted first), Haifushi (Pumice) 30g (decocted first), Haizao (Sargassum) 30g, Kunbu (Laminaria) 30g.
Compound Banmao Capsule (Guizhou Yibai).
Xihuang Wan (Beijing Tongrentang): once daily, before sleep, dose 3-12g.
Jinkui Shenqi Wan.
Pingxiao Pian.
Later, because urinary retention occurred after taking painkillers, the prescription was adjusted as follows:
Zhuling 30g, Fuling 30g, Zexie 15g, Huashi (Talc) 15g (wrapped), Ejiao (Donkey-Hide Gelatin) 15g (taken in three divided doses), Qianghuo (Notopterygium) 10g, Duhuo (Angelica Pubescens) 10g, Jianghuang (Turmeric) 6g, Chao Jiangcan (fried Bombyx) 10g, Chanyi (Cicada Slough) 6g, Chaihu (Bupleurum) 10g, Huangqin (Scutellaria) 10g, Wuweizi (Schisandra) 15g, raw Dahuang (Rhubarb) 10g (added later).
June 5, 2017
After two Opdivo treatments, the patient had severe swelling and intense pain, intolerable. After taking the decoction, pain was markedly reduced and she could sleep; before the decoction she could not sleep at all. But she sweats a lot; clothes are wet.
The patient is cold-intolerant, covers herself with a thick quilt to sleep. Right pulse: slippery, rapid, forceful; left pulse: deep, fine, rapid. Tongue pale with thin white coat and teeth marks. Back pain reduced.
Prescription: Zhuling 30g, Fuling 30g, Zexie 15g, Huashi 15g (wrapped), Ejiao 15g (in three divided doses), Qianghuo 10g, Duhuo 10g, Jianghuang 6g, Chao Jiangcan 10g, Chanyi 6g, Chaihu 6g, Huangqin 6g, Wuweizi 15g, Dibiechong (Eupolyphaga) 10g, Taoren (Peach Kernel) 10g (added later), raw Dahuang 10g (added later), raw Huangqi 30g, Chao Baizhu (fried Atractylodes) 30g, Han Fangji 30g, Fangfeng (Saposhnikovia) 10g, Yinchen (Artemisia Capillaris) 20g, Cheqiancao 15g, Huainiuxi 15g, Duzhong (Eucommia) 10g, Xuduan (Dipsacus) 10g, Pugongying 30g, Jinyinhua 30g (added later), Yejuhua 10g, Tiankuizi 10g, Diding 10g, Yiyiren 60g, Xuanshen 15g, Zhebeimu 15g, raw Muli 30g (decocted first), Haifushi 30g (decocted first), Haizao 30g, Kunbu 30g, Baidoukou (Amomum) 10g, Huoxiang 10g, Peilan 10g, Shudi (Prepared Rehmannia) 30g, Paofuzi (processed Aconite) 10g (decocted first), Cangzhu (Atractylodes) 15g, Houpo (Magnolia Bark) 15g, Baiji 15g, Fengweicao 15g.
June 21, 2017
After the previous medicine, pain had basically disappeared, edema gone. White blood cells dropped, CEA fell markedly. Liver and kidney function not good. Stomach vaguely aches; no heartburn. Stool dry and bound; with enema she has a formed bowel movement daily. WBC low; recovered after a WBC-boosting injection. RBC and platelets low, hemoglobin low. Sweats after medicine. Pulse: deep, fine, rough.
Pugongying 30g, Jinyinhua 30g (added later), Yejuhua 10g, Tiankuizi 10g, Diding 10g, Xuanshen 15g, Zhebeimu 15g, raw Muli 30g (decocted first), Haifushi 30g (decocted first), Haizao 30g, Kunbu 30g, Pian Jianghuang 6g, Chao Jiangcan 10g, Chanyi 6g, Dibiechong 10g, Taoren 10g (added later), raw Dahuang 10g (added later), Maidong (Ophiopogon) 10g, Tiandong (Asparagus) 10g, Shengdi (Raw Rehmannia) 12g, Danggui (Angelica) 12g, Chuanxiong (Ligusticum) 10g, Chaihu 10g, Huangqin 10g, Wuweizi 15g, Fengweicao 15g, Xiaoji 15g, Daji 15g, raw Huangqi 60g, Roucongrong (Cistanche) 60g, Huomaren (Cannabis Seed) 30g, Chao Jineijin (fried Gizzard Lining) 30g (added later), Jiao Sanxian each 15g, Duzhong 10g, Xuduan 10g, Tusizi (Cuscuta) 10g, Shayuanzi 10g, Nüzhenzi 10g, Mohanlian 10g, Sanleng (Sparganium) 6g, Ezhu (Curcuma) 6g, Honghua (Safflower) 3g, Chao Zhizi (fried Gardenia) 10g, Mudanpi (Moutan Bark) 10g, Yiyiren 60g.
Patent medicine: Pingxiao Pian, three times daily, 4-8 tablets each time.
My self-formulated anti-cancer Sanjie powder: 1-2g each time, stirred in water, twice daily.
July 7, 2017
Recently PD-1 (still Opdivo) was used again. Lower abdomen bloated, legs swollen. Since yesterday, lower genital bleeding. Appetite good, abdomen bloated, stool not passing. Pulse: deep, fine, moderate.
Decoction: raw Huangqi 30g, Dangshen (Codonopsis) 20g, Fuling 20g, Chao Baizhu 30g, Zhi Gancao (Honey-fried Licorice) 10g, Chenpi 10g, Qingpi (Unripe Tangerine Peel) 10g, Houpo 20g, Cangzhu 20g, Shudi 15g, Danggui 10g, Chuanxiong 10g, Baishao (White Paeony) 15g, Bajitian (Morinda) 15g, Yinyanghuo (Epimedium) 15g, Xianlingpi (Epimedium) 15g, Tusizi 15g, Shayuanzi 15g, Zhuling 20g, Han Fangji 20g, Huainiuxi 15g, Cheqianzi (Plantago Seed) 15g, Duzhong 10g, Xuduan 10g, Chaihu 10g, Huangqin 10g, Wuweizi 15g, Chao Zhizi 10g, Yinchen 20g, Nüzhenzi 10g, Mohanlian 10g, Yiyiren 60g, Fengweicao 15g, Shengdi 24g, Maidong 24g, Xuanshen 30g, Xianhecao (Agrimonia) 30g, Fengweicao 30g, Baiji 20g, Daji 20g, Xiaoji 20g, Jiao Sanxian each 15g, Chao Jineijin 30g, Lianqiao (Forsythia) 15g, Zhebeimu 15g, raw Muli 30g (decocted first), Haifushi 30g (decocted first).
Patent medicines: as before.
Follow-up, July 16, 2017
Appetite good, abdominal bloating much reduced, stool still not passing. Legs walk better than last time; legs numb. Pulse: deep, fine, moderate. Hands and feet cold; easy subcutaneous bleeding.
Decoction: raw Huangqi 60g, Dangshen 20g, Fuling 20g, Chao Baizhu 30g, Zhi Gancao 10g, Chenpi 10g, Qingpi 10g, Houpo 15g, Cangzhu 15g, Shudi 15g, Danggui 12g, Chuanxiong 10g, Baishao 15g, Bajitian 15g, Xianlingpi 15g, Tusizi 15g, Shayuanzi 15g, Han Fangji 20g, Huainiuxi 10g, Cheqianzi 10g, Duzhong 10g, Xuduan 10g, Chaihu 10g, Huangqin 10g, Wuweizi 15g, Nüzhenzi 10g, Mohanlian 10g, Huangjing (Polygonatum) 15g, Yiyiren 60g, Xianhecao 30g, Fengweicao 30g, Baiji 20g, Daji 20g, Xiaoji 20g, Jiao Sanxian each 15g, Chao Jineijin 30g, Lianqiao 15g, Xuanshen 15g, Zhebeimu 15g, raw Muli 30g (decocted first), Haifushi 30g (decocted first), Ganjiang (Dried Ginger) 30g, Rougui (Cinnamon Bark) 30g, Guizhi (Cinnamon Twig) 30g, Shengjiang (Fresh Ginger) 30g, Mugua (Quince) 20g, Dazao (Jujube) 10 pieces, Fangfeng 10g, Zhi Shouwu (processed Polygonum) 30g.
Patent medicines: basically as before.
Follow-up, August 7, 2017
Pulse: soft, feeble, fine, rapid. The patient recently took Western medicine for constipation and developed stomach pain.
Formula 1
Chaihu 12g, Yujin 12g, Xiangfu 12g, Muxiang 6g, Chenpi 6g, Binglang 10g, Foshou 12g, Wuyao 12g, Huoxiang 6g, Chao Baizhu 15g, Zhi Gancao 6g, Laifuzi 30g, Danggui 12g, Baishao 12g, Fangfeng 15g, Baizhi (Angelica Dahurica) 12g, Jingjie (Schizonepeta) 10g, Manjingzi (Vitex) 10g, Chuanxiong 10g, Hupo Fen (Amber Powder) 3g (in two divided doses), Danshen (Salvia) 20g, Dannanxing (Bile Arisaema) 10g, Rougui 10g, Shengma (Cimicifuga) 10g, Qianghuo 10g, Ruxiang (Frankincense) 8g, Moyao (Myrrh) 8g, Shengjiang 3 slices, Dazao 5 pieces, Tianma (Gastrodia) 10g, Gouteng (Uncaria) 15g, Gouqi (Goji) 30g, Duzhong 10g, Xuduan 10g, Shayuanzi 10g, Tusizi 10g, Bajitian 10g, Xianlingpi 10g.
Formula 2
Pugongying 30g, Rendongteng (Honeysuckle Stem) 30g, Yejuhua 10g, Diding 15g, Tiankuizi 10g, Tengligen (Actinidia Root) 30g, Daxueteng (Sargentodoxa) 30g, Dongguaren (Winter Melon Seed) 30g, Yiyiren 30g, Xiaoji 12g, Daji 12g, Banzhilian (Scutellaria Barbata) 15g, Baihua She Shecao (Hedyotis) 15g, Machixian (Purslane) 30g, Yuxingcao (Houttuynia) 6g, Xuanshen 12g, Zhebeimu 12g, raw Muli 30g, Haizao 30g, Kunbu 30g, Gouqi 30g, Duzhong 10g, Baishao 12g, Danggui 12g, Xuduan 10g, Shayuanzi 10g, Tusizi 10g, Bajitian 10g, Xianlingpi 10g.
One dose daily; Formula 1 on odd days and Formula 2 on even days; take 4 days then rest 1-2 days.
Patent medicines: as before.
August 16, 2017
Pulse: deep, fine, weak. Tongue: red, moist, with yellow greasy coat. Stomach occasionally aches vaguely.
Decoction: Pugongying 30g, Rendongteng 30g, Yejuhua 10g, Diding 15g, Tiankuizi 10g, Tengligen 30g, Daxueteng 30g, Dongguaren 30g, Yiyiren 30g, Lianqiao 15g, Chixiaodou (Adzuki Bean) 30g, Xiaoji 12g, Daji 12g, Banzhilian 15g, Baihua She Shecao 15g, Machixian 30g, Yuxingcao 6g, Xuanshen 12g, Zhebeimu 12g, raw Muli 30g, Haizao 30g, Kunbu 30g, Gouqi 30g, Duzhong 10g, Baishao 12g, Danggui 12g, Xuduan 10g, Shayuanzi 10g, Tusizi 10g, Bajitian 10g, Xianlingpi 10g, Mohanlian 10g, Nüzhenzi 10g, Shashen 10g, Maidong 15g, Tiandong 15g, Wuweizi 15g, Tianma 15g, Gouteng 15g, Shancigu (Cremastra) 6g, Sanleng 6g, Ezhu 6g, Chaihu 10g, Huangqin 10g, Roucongrong 30g, Jiao Sanxian each 15g, Chao Jineijin 30g, Mudanpi 10g, Taoren 10g, Baiji 15g, Xianhecao 30g, Fengweicao 30g.
Patent medicines: as before.
After PD-1 (the trial drug was Opdivo), this patient developed severe side effects: edema, intense pain, and severe constipation (the constipation was later resolved by adding 30g each of Mangxiao and Dahuang). Without TCM supportive care, she could not have completed PD-1 at all.
Throughout, I used large amounts of raw Huangqi; far from causing severe side effects, it helped the patient solve a series of problems. After PD-1, the patient herself said she never imagined PD-1's side effects would be so much greater than chemotherapy's.
After later encountering several patients who died from PD-1 side effects, I am convinced that if this patient had not received appropriate TCM as supportive therapy, she could not have survived such severe adverse effects.
Treated with PD-1 combined with my pattern-differentiation formulas and anti-tumor formulas, she did well: the tumor basically cleared, and all cancer markers fell within normal range. She now lives normally.
PD-1, as a new cancer treatment, has indeed brought hope to some late-stage patients. But its side effects have not received enough attention. At present, neither Chinese nor Western medicine has as much experience managing PD-1 side effects as it does with chemo-radiation. There is a special need for open discussion of PD-1's adverse effects and how to manage them.
I wrote this article with no intention of rejecting PD-1 as a new therapy. It is just that among cancer patients, some have too little knowledge of the side effects and risks of PD-1 or PD-1 plus chemo, and are overly optimistic. Because some patients and doctors underestimated the side effects, patients died rapidly after starting PD-1.
I hope this article collects more real PD-1 treatment data from patient feedback as a clinical reference, and corrects some unfounded prejudices. I will continue to follow PD-1 and, when the time is right, publish more articles discussing my TCM thinking on treating its side effects.