大力出奇迹（一）

一、大剂量辅酶Q10治疗乳腺癌

上世纪90年代初期丹麦进行了一项用包括辅酶Q10在内的营养套餐辅助治疗高危乳腺癌患者的临床试验。先后发了三篇论文，记录了试验组的治疗结果尤其是随着辅酶Q10剂量调整加大后入组患者治疗结果的变化。
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3 R9 G! X2 ^: e! W- k1、《Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10》

这个试验组入组了32-81岁的32名乳腺癌患者。这些乳腺癌患者都有淋巴结转移，有些有胸壁、皮肤、骨、肝等部位转移。

, `! \) w" D2 ]8 k这些患者原定计划的治疗--进行放、化疗、手术、他莫昔芬内分泌等常规治疗（当时还没有靶向药、icb免疫这些），正常进行。在此基础上，所有患者全都增加癌症辅助营养干预方案(ANICA方案)。有几位患者在本身还有病灶或者积液的情况下放弃了常规治疗，只吃这个癌症辅助营养套餐。
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ANICA方案包括： (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day).

试验方案设计的时候，研究者根据1988年的统计数据分析预估，入组18个月时，这32名高危患者中会有4人死亡；24个月的时候，会有6人死亡。
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结果试验结果：
(1) none of the patients died during the study period. (the expected number was four.)

, c6 V( y+ m6 h& w(2) none of the patients showed signs of further distant metastases.

(3) quality of life was improved (no weight loss, reduced use of pain killers).

(4) six patients showed apparent partial remission.
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结果出乎意料的好。

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2、《Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10》
7 R" p: v  v$ w9 [5 [( Z7 Q这篇论文分析了上面那个临床试验24个月时CR的那两名患者的情况，认为CR的原因是这两位患者大幅提高了辅酶q10的剂量，从原来的每天90毫克吃到了每天300-390毫克。

“Six of the 32 patients showed partial tumor regression. In one of these 6 cases, the dosage of CoQ10 was increased to 390 mg. In one month, the tumor was no longer palpable and in another month, mammography confirmed the absence of tumor. Encouraged, another case having a verified breast tumor, after non-radical surgery and with verified residual tumor in the tumor bed was then treated with 300 mg. CoQ10. After 3 months, the patient was in excellent clinical condition and there was no residual tumor tissue. The bioenergetic activity of CoQ10, expressed as hematological or immunological activity, may be the dominant but not the sole molecular mechanism causing the regression of breast cancer.”
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7 ?7 C4 X7 L( a( ~, z. ~' ^辅酶q10的说明书常规剂量是每天30毫克左右；试验组入组患者后期吃每天300-390毫克，确实是大剂量了。
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9 ^( h; ]  p( [9 |  K1 Y5 x3 |3、《Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases》
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. ]3 G% _$ G& s# f9 _2 l# p这篇论文讲上面那个试验随着提高辅酶Q10的剂量后，陆续又有三位患者达到了CR。24个月的时候，不但没有患者死亡（试验设计预估是6人死亡），还有5位患者达到了CR。

“Over 35 years, data and knowledge have internationally evolved from biochemical, biomedical and clinical research on vitamin Q10 (coenzyme Q10; CoQ10) and cancer, which led in 1993 to overt complete regression of the tumors in two cases of breast cancer. Continuing this research, three additional breast cancer patients also underwent a conventional protocol of therapy which included a daily oral dosage of 390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during the complete trials over 3-5 years. The numerous metastases in the liver of a 44-year-old patient "disappeared," and no signs of metastases were found elsewhere. A 49-year-old patient, on a dosage of 390 mg of vitamin Q10, revealed no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75-year-old patient with carcinoma in one breast, after lumpectomy and 390 mg of CoQ10, showed no cancer in the tumor bed or metastases. Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 micrograms/ml increased to 3.34-3.64 and to 3.77 micrograms/ml, respectively, on therapy with CoQ10 for patients A-MRH and EEL.”
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5位CR患者都是每天用90毫克辅酶Q10时有获益，但达不到CR；把辅酶Q10加到每天300-390毫克后，短时间内都达到了CR。

不过有一点要注意。有一些研究认为，辅酶Q10这样的抗氧化剂，会削弱细胞毒性化疗药物的作用，反而给乳腺癌治疗带来不利影响。

不过仔细看那些认为辅酶Q10有可能会给乳腺癌治疗带来不利影响的研究，要么还是动物研究；要么是样本量非常小；最关键是剂量上，那些研究的辅酶Q10用的都是正常剂量小剂量，没有用300-390毫克这样的大剂量。所以说服力不足。抗癌用药，药物的剂量、剂型、给药方式、给药频率这些量发生一点变化，试验结果就有可能完全不同。
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! Q9 ^, w, H; K) A3 Z虽然这5位CR患者，是有4位患者除了吃包括辅酶Q10在内的ANICA方案外没有同时做放化疗手术等常规治疗；另外1位CR同时在用他莫昔芬，这是内分泌药物，也不是细胞毒性化疗药物。但是，整个试验组32名患者，用了大剂量辅酶Q10后，是全部获益的。那些虽然没有CR但也获益的患者，绝大多数都是同时在做放化疗这些常规治疗的。
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二、大剂量甲地孕酮治疗晚期耐药乳腺癌
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《大剂量甲孕酮治疗晚期耐药乳腺癌的效果评价》

- N% m8 ^' O  b& ~9 z5 v0 y) ~“25例晚期乳腺癌患者，年龄48（35～70）岁。转移部位：骨转移17例，肺转移8例，胸壁软组织7例，胸腔积液5 例，肝转移5例，骨髓转移3例，脑转移2例。入组患者均为手术后复发转移，化疗无效或耐药，他莫昔芬和芳香化酶抑制剂无效者。”
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“给药：甲孕酮口服500mg／次，2次／d”

“CR 2例（8％），PR 6例（24％），SD 4例（16％，其中3例 SD≥6月），PD 13例（52％）。临床控制率为48％，临床获益率44％。中位病变进展时间为7（2～27）个月，有效病例的显效时间为5～14d。 ”

" a% L% Q6 ^  \6 |“在服用甲孕酮之前接受了多组化疗药物及至少一种内分泌治疗后耐药（即五线及以上）的患者还可达到36∙4％的临床获益率”
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“尽管高于雌激素受体（ER）、孕激素受体（PR）阳性患者的获益率明显 ER、PR 均阴性的患者，但在后者中也获得了20％的疗效。”

“本组骨和肺转移患者有较高的获益率”
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“在有软组织、胸腔、 肝等部位转移的患者中取得的疗效相对较差。在2例脑转移的
患者（1例伴肺、骨转移‚另1例伴胸膜、肝转移）中无效。 ”
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7 n" y: C0 Y% Z% t. ^* F3 \“所有患者服药后未出现肝肾功能损害，未见白细胞、血小板下降。毒副作用包括：向心性肥胖4例，阴道出血5例，下肢静脉血栓1例。”

) F4 b, P* Q' Z4 w1 G“ 甲地孕酮对骨转移有较好的疗效”
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4 ~7 `  A! G: F三、大剂量他莫昔芬治疗乳腺癌患者的骨转骨痛
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7 r7 Q) R$ }4 c+ V5 t之前介绍过大剂量他莫昔芬发挥p-gp蛋白抑制剂作用给多西他赛提高疗效的临床试验。这里再介绍一个大剂量他莫昔芬治疗乳腺癌患者的骨转骨痛的临床试验。

《Bone metastasis in breast cancer is treated by high-dose tamoxifen》这篇论文讲了一个对他莫昔芬已经耐药的乳腺癌骨转移患者再单用大剂量他莫昔芬治疗骨转骨痛的临床试验。
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招募了28名乳腺癌有骨痛的骨转患者（26名已经绝经），这些患者之前都接受过内分泌治疗，有些患者之前接受过正常剂量的他莫昔芬（每天20毫克）治疗已经耐药了，有些患者用过唑来膦酸等保骨针。
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现在大剂量单药他莫昔芬：Tamoxifen was administered as monotherapy. The initial dose was 100 mg (5 tablets x 20 mg) daily for two weeks. During this two-week period, pain reduction was
, o3 z0 _; f9 L- X; |the main criterion for determining a response and for treatment continuation. After these two weeks, if there was a response in pain, the dose of tamoxifen was reduced to 80 mg daily for an additional three weeks, followed by 60 mg for 3 weeks and then 40 mg daily for at least two
- R- h% g: }: e2 Amonths and eventually 20 mg daily for 1-2 years. 先每天100毫克他莫昔芬吃2周；如果吃下来骨痛减轻了，那继续用他莫昔芬单药，变成80毫克吃3周；接着60毫克吃3周；接着40毫克至少吃两个月；最后变成20毫克每天吃1-2年。
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他莫昔芬治疗乳腺癌的说明书常规剂量是每天20-40毫克。试验组的这个下坡剂量前期是超过常规剂量的比较高的剂量。
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2 r0 `; ?9 U. }, t! A4 F( [试验结果：Twenty six out of 28 patients (median age 66 years, range 29-83), were postmenopausal and were included in the study. No patient had metastatic disease in other organs apart from the skeleton. Twenty six out of 28 (92.8%) patients responded to treatment, the criteria being mainly pain reduction, and body mobilization (an amelioration which lasted 8 months-4 years). In 15 patients on treatment for over a year a bone scan showed disappearance of osteolysis of a single bone me tastasis (Figures 1 and 2). Four patients who had disease recurrence with pain after 12-18 months, repeated the high-dose tamoxifen treatment with positive results (pain reduction).28名患者中有26名患者有疗效，骨痛减轻，能自由活动，改善时间是8-48个月。26名有效的患者中，有15人，治疗一年多后检查，一些溶骨性骨转病灶消退了。有4名有效的患者，在12-18个月后又开始骨痛；从头开始每天100毫克吃2周这样重复治疗过程，骨痛又减轻了。

! u) c8 ^# y8 f4 G5 B* T5 R疗效非常好，尤其是在患者原先他莫昔芬已经耐药了的情况下显得极为突出。