Dichloromethylene-Diphosphonate in Patients with Prostatic Carcinoma Metastatic to the Skeleton

Abstract

A total of 17 patients with multiple osteoblastic bone metastases owing to prostatic carcinoma was treated with 2-dichloromethylene-diphosphonate, a powerful inhibitor of bone resorption. The drug was given intravenously (300 mg.) for 2 weeks and then orally (3,200 mg.) or intramuscularly (100 mg.) for 4 to 11 weeks. A definite improvement in pain, assessed by daily consumption of analgesic drugs and by an analogic scale, was observed within 10 days in 16 of the 17 patients. Four patients confined to bed rest for pain were able to walk after 2 weeks and reversal of paralysis also was noted in 1 patient. Transient changes in serum calcium (decreasing) and alkaline phosphatase (increasing) were observed in most patients. In the 3 patients in whom it was performed, repeated bone scanning showed a partial regression of pathological areas in 2 and the complete disappearance of most pathological areas in 1. Our results suggest that 2-dichloromethylene-diphosphonate may represent an important supportive treatment in patients with bone metastases owing to prostatic carcinoma, providing sustained relief of pain and regression of bone destruction without undesirable side effects.

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

“…While NBPs act inside cells, inhibiting the mevalonate cycle, nonNBPs act by promoting direct cytotoxicity towards osteoclasts and osteoblasts, thereby inducing apoptosis and inhibiting the ATP/ADP translocase enzyme. 13,14 The differences in pharmacological action between the groups determine their effects on the inflammatory process. Non-NBPs such as clodronate have anti-inflammatory action and antirheumatic activity, whereas this is not well established in NBPs.…”

“…Non-NBPs such as clodronate have anti-inflammatory action and antirheumatic activity, whereas this is not well established in NBPs. 14 Preclinical studies have demonstrated that osteolytic lesions always precede the abnormal bone deposition (osteoblastosis) that gives the osteoblastic appearance to the majority of metastatic skeletal lesions from prostate cancer. 7 It has been shown through biopsies of metastatic skeletal lesions that excessive bone absorption occurs at these sites, in the same way as it occurs in breast cancer.…”

“…A significant improvement in 16 patients (94.1%) was observed, in relation to pain and Karnofsky's index, for 4-8 weeks. 14 Vorreuther 15 administered intravenous clodronate to 41 patients with skeletal lesions due to prostate cancer, at a dosage of 300 mg daily for 8 days, along with 1600 mg orally. It was observed that 20 patients (71%) presented significant reduction in pain as early as the first 3-5 days, with nine patients continuing to show response thereafter.…”

Advances in the use of bisphosphonates in the prostate cancer setting

“…A reduction in skeletal morbidity was usually reported. There were initially rather fewer studies in the prostate cancer setting, although some early work showed reductions in bone pain with clodronate, 43,44 although this was not later borne out in randomised studies with this drug. 45,46 Early small-scale studies with pamidronate provided encouraging signs of its potential benefit, 47,48 but it was several years before a well-designed randomised study was published on the use of later-generation bisphosphonates in prostate cancer.…”

Concomitant i.v. and oral clodronate in the relief of bone pain – a double-blind placebo-controlled study in patients with prostate cancer

“…Only two of the limited number of studies on treatment of painful bone metastases due to prostate cancer with clodronate (Adami et al, 1985;Adami et al, 1989;Elomaa et al, 1992;Vorreuther et al, 1992;Vorreuther, 1993;Kylmala et al, 1994;Cresswell et al, 1995) have been placebo controlled (Adami et al, 1989;Elomaa et al, 1992). Adami and colleagues (1989) first showed, in 13 patients, that intravenous administration of clodronate was more effective in reducing bone pain than oral administration and that the effect lasted longer when intravenous administration was followed by oral treatment.…”