Chlorophyll Derivative Based Photodynamic Therapy (PDT) For Hormone Refractory Prostate Cancer

BackgroundIn 1941, Dr Charles B. Huggins in collaboration with his students Clarence V. Hodgesand William W. Scott demonstrated androgen dependence of prostate cancer. Thedecrease of androgen could cause regression of prostate tumors. Androgen blockade isthe primary therapy for locally advanced and metastatic diseases. Androgenblockade could relieve metastatic presentations and decrease PSA to nadir. Afterseveral months to years, PSA increased again and signs progressed. Though serumandrogen was still in the castrate level, prostate cancer has progressed. Thisandrogen resistance is so called hormone refractory prostate cancer (HRPC).Photodynamic therapy (PDT) is based on the relatively old concept that lightirradiation can change an inert substance to an active one. Current PDT involves theinteraction of a specific light-sensitive agent, the so-called photosensitizer, and lightof a particular wavelength in an oxygenated environment. The light energy isabsorbed by the photosensitive molecules and 'activates'them. The activatedmolecule transfers an electron to an adjacent oxygen molecule and produces oxygenradicals or the energy is transferred from the activated photosensitive molecule to anoxygen, generating an excited singlet oxygen molecule. These reactive oxygenspecies have a very short life time, but are extremely reactive and ussually induce acytotoxic or cell destruction, respectively. Other, more macroscopic effects likevascular damage and possibly immunologic reaction contribute to the final tissuedamage, probably to a wide extent.Chlorophyll Derivative, a new photosensitizer extracted from excrementum bombysisunder the project of "the seventh-five year research "is applied with semiconductorlaser in this study. The effect of PDT for hormone refractory prostate cancer andpathological changes of the normal prostate after laser irradiation are observed. Thepractical methods of PDT are considered for the potential of clinical practice. 7复旦大学博士毕业论文Part I Considerations in Combined Androgen Blockade for Prostate CancerObjectives: Some clinical issues were reviewed and considered on the practice ofcombined androgen blockade(CAB), including PSA nadir after bilateral orchiectomyand orally flutamide, liver dysfunction and relative treatment, the relief of bonemetastasis and pain.Methods: One hundred fifty-three patients with pathologically confirmed prostatecancer from June,1997 to June,2001 were blocked with bilateral orchiectomy andorally flutamide and reviewed. The average age was 73.8(63-85) and average PSAwas 71.4ng/ml (from 11.5ng/ml to >250ng/ml). Ten patients were in stage B2, fortyseven patients in stage C and ninety-six others in Stage D. PSA alterations wereobserved at month 1,3 and 6 after CAB. Twenty-three patients among them whooccurred live dysfunction were reviewed of hepatitis history. Seventy-twoorchiectomized patients and seven others with leuprorelin were observed on the effectof radionuclide for bone metastasis in three comparative groups: 46 cases of CAB, 21cases of CAB plus strontium-89(Sr 89) and 12 cases of CAB plus 153SM-EDTMP.Results:1,The percentage of patients with PSA less than 0.5ng/ml after CAB was79.3%(69/87 ) at month 1, 91.3%(137/150) at month 3 and 88.9%(113/127) at month6. PSA was continuously increasing(>10ng/ml) at three months to two years in 14others whose PSA was more than 0.5ng/ml at month 6 after CAB compared with the 7similar increases among 139 contemporary patients with PSA <0.05ng/ml(p<0.001).PSA <0.05ng/ml was unrelated to the pretreatment level and clinical stage(p>0.05).2,Twenty-three patients occurred liver dysfunction at month 6.2 (from 3 to 12months). Seventeen patients occurred transient dysfunction with only ALT increaseand normal total bilirubin. After one to two months of first-line option withoutdiscontinuation of flutamide, the level of ALT recovered. Six patients with severe...