Clinical Topics & News
Effective Treatment Options for Metastatic Pancreatic Cancer
A discussion on new and emerging treatments for patients with metastatic pancreatic cancer.
The RTOG study was a randomized clinical study comparing various radiation schedules; 1,500 cGyin 1 week; vs 2,000 cGy in 1 week; vs 2,500 cGy in 1 week; vs 3,000 cGy in 2 weeks; or 4,050 cGy in 3 weeks. The conclusion was that local radiotherapy was an effective therapy for symptomatic and palliative therapy of bone metastases. Furthermore, low-dose radiotherapy was as good as various higher dose protracted courses of radiation treatments in terms of overall response rates (ORRs).24
Nearly 96% of patients eventually reported minimal pain relief to their palliative course of radiotherapy and experienced at least some pain relief within 4 weeks of radiation therapy. Complete pain relief was attained in 54% of patients regardless of the radiation dose-fraction schedules used. The median duration of complete pain response was about 12 weeks; > 70% of patients did not experience relapse of pain.26
Hartsell and colleagues investigated the efficacy of 800 cGy in a single fraction compared with 3,000 cGy in 10 fractions as part of a phase 3 randomized study of symptomatic therapy for pain palliation.27 The results showed 66% ORRs with similar complete and partial response rates (RRs) for both radiation groups. The complete RRs were 15% in the 800 cGy single-fraction arm vs 18% in the 3,000 cGy therapy arm, whereas partial RRs were 50% and 48% in the single vs the 3,000 cGy arms, respectively. However, there was a higher rate of retreatment for patients treated with the 800 cGy single-fraction radiotherapy. The 800 cGy single-fraction radiotherapy program seems rather popular in Canada and in European countries but is currently not widely used in the U.S.
Surgical Therapy
The surgical indications for managing bone metastases can vary, depending on disease location, surgeon’s preference, and patient’s overall disease status and related morbidities. Pain relief of fractured long bones (humerus, femur, or tibia) is crucial. The main goals of surgical intervention in these cases include the restoration of stability and functional mobility, pain control, and improving QOL. Weight-bearing bones (humerus/tibia) are especially at risk of bone fracture, and compromise of these is an indication of surgery. Postoperative external-beam radiation is recommended in most cases to eradicate residual microscopic disease or tumor progression.28
Radiopharmaceutical Therapy
Bone-seeking radiopharmaceuticals are effective and have been widely used for pain palliation. The usual indications for radiopharmaceutical therapy include diffuse osteoblastic skeletal metastases demonstrated on bone scan, painful bone metastases not responding well to analgesics, and hormone-refractory metastatic prostate cancer. At present, strontium-89 (Sr-89), samarium-153 (Sm-153), phosphorus-32 (P-32), and radium 223 dichloride are radionuclides currently accepted as attractive therapeutic modalities for pain management (Table 2).
The clinical response is not immediate, and the average time to response is 1 to 2 weeks, but sometimes much longer. The main adverse reaction of systemic radiopharmaceutical therapy is myelotoxicity, such as thrombocytopenia and/or leukopenia. Occasionally, a so-called flare phenomenon of a transient pain increase may develop as well.29,30
Systemic Pharmacotherapy
Bisphosphonates are drugs commonly used to treat bone metastases. The benefits of bisphosphonate therapy are bone pain relief, the reduction of bone destruction, and the prevention of hypercalcemia and bone fractures. Bisphosphonates are typically more effective in osteolytic metastases and easily bind to bone, inhibiting bone resorption and increasing mineralization.31,32 Also, recent clinical studies suggest that bisphosphonates may inhibit tumor progression of bone metastases.
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Zoledronic acid is currently one of the most potent bisphosphonates and is effective in most types of metastatic bone lesions.33 Denosumab, another drug, diminishes osteoclast activity, leading to decreased bone resorption and increased bone mass.34,35 Denosumab is useful in preventing complications as a result of bone metastases from solid tumors and has been recently approved by the FDA for treatment of postmenopausal osteoporosis and the prevention of skeletal-related events (SREs) in cancer patients with bone metastases.
Adverse Effects
Zoledronate and bisphosphonates in general are not recommended for patients with kidney disease, including hypocalcaemia and severe renal impairment. A rare but well-known complication of bisphosphonate administration is osteonecrosis of the jaw, which is somewhat more common in MM, especially after dental extractions. General nonspecific adverse effects include fatigue, anemia, muscle aches, fever, and/or edema in the feet or legs. Flulike symptoms and generalized bone discomfort can also be seen shortly after the first infusion (Table 3).
Breast Cancer
Bisphosphonates have been shown to effectively prevent SREs in breast cancer patients with bone metastases.36 For example, zoledronic acid is the most effective bisphosphonate and has been demonstrated to significantly delay the time to development of a first SRE, reducing the overall SRE rate by 43%.37
