Journal of Clinical Oncology, Vol 10, 591-598, Copyright © 1992 by American Society of Clinical Oncology
Treatment of bone metastases with dichloromethylene bisphosphonate
G Francini, S Gonnelli, R Petrioli, F Conti, P Paffetti and C Gennari
Division of Medical Oncology, University of Siena, Italy.
PURPOSE: The study was undertaken to evaluate the effects of
dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic
bone lesions from a variety of tumoral primary sites and to investigate the
in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS:
Seventy-six patients participated in the current study: 59 had
predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen
patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP
intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly
(IM) for 14 days. Biochemical parameters were measured in the patients
before the start of treatment and 3, 7, 14, and 21 days after beginning
treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with
predominantly osteolytic lesions were then randomized to receive
chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at
an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS: Serum calcium
(Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP)
excretion levels significantly decreased in all patients, whereas no
significant changes occurred in serum alkaline phosphatase (AlkPh) and bone
Gla- protein (BGP) levels. In 56 patients with painful bone lesions, a
progressive analgesic effect was observed mainly between day 7 and day 14.
In patients with predominantly osteoblastic metastases, the Cl2MDP
treatment led to a more evident hypocalcemia and an increase in both AlkPh
and BGP. However, in the majority of these patients the hypocalcemia was
corrected by the concurrent use of effective cytotoxic treatments capable
of reducing osteoblast stimulation. During 6 months of follow-up, two
pathologic fractures occurred in patients of group A, and none occurred in
patients of group B. CONCLUSIONS: We conclude that Cl2MDP was effective in
patients presenting bone metastases with and without hypercalcemia. Care
should be taken particularly in those patients with mixed metastases when
the sclerotic component is predominant, as the drug may enhance the
possibility of hypocalcemia, which is generally corrected by effective
cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in
the treatment of bone metastases.
