Bone Tumors: Drug Therapy

Therapeutic targets

• Relief of pain
• Stabilization of bone sections at risk of fracture
• Prevention or improvement of existing neurological deficits in bone tumors in the skull or vertebrae.
• Reduction of tumor size – preoperatively (before surgery) by radiotherapy (radiotherapy) or chemotherapy (neoadjuvant chemotherapy).
• Removal of the tumor – see “Surgical therapy“.
• Healing

Therapy recommendations

Therapy depends on the type and extent of the bone tumor. In most cases, therapy consists of a combination of radiotherapy (radiotherapy), surgery, and chemotherapy (synonym: cytostatic therapy).

• Analgesia according to WHO staging scheme:
  • Non-opioid analgesic (paracetamol, first-line agent).
  • Low-potency opioid analgesic (e.g., tramadol) + non-opioid analgesic.
  • High-potency opioid analgesic (eg, morphine) + non-opioid analgesic.
• Chemotherapeutic agents are used as an independent form of therapy with a curative (curative) or palliative (palliative; without a curative approach) approach in the treatment of the following malignant (malignant) bone tumors:
  • Osteosarcoma
  • Ewing’s sarcoma
  • Plasmocytoma/multiple myeloma
  • Bone metastases
• Chondrosarcomas respond poorly to chemotherapy and radiatio (radiation therapy), making surgical removal the only treatment option.
• Osteoid osteomas:
  • Osteoid osteoma-related pain responds very well to nonsteroidal anti-inflammatory drugs (NSAIDs) such as salicylates, e.g. acetylsalicylic acid (“ASA-sensitive”). In half of the cases, a decrease in pain can be observed.Caution: Salicylates are not recommended for permanent medication due to the risk of gastrointestinal bleeding (bleeding in the gastrointestinal tract)!
  • About the administration of cyclooxygenase inhibitors can inhibit the production of prostaglandins (= “pain substance”) by osteoblasts in the nidus (focus of osteoid osteoma).

Therapy recommendations for osteosarcoma (primary malignant).

• due tohigh risk of metastases (daughter tumors) and to reduce the tumor mass before surgery, chemotherapy (= neoadjuvant chemotherapy; induction chemotherapy) is given according to therapy protocol (therapy optimization studies; COSS: Cooperative Sarcoma Study of the GPOH; EURAMOS. European and American Osteosarcoma Study; EURO-B.O.S.S. : for elderly patients (41-65 years)).
  • Duration: up to 10 weeks
  • Note: Patients with painful spontaneous fracture may not require preoperative chemotherapy.
• Subsequently tumor extirpation (surgical removal of the tumor) (> 80% of patients can be operated arm and leg preserving).
• Postoperatively, further chemotherapy is given (= adjuvant chemotherapy).
  • Duration: up to 10 weeks: up to 18 weeks.
• Osteosarcomas are not very sensitive to radiation.

Therapy recommendations for Ewing’s sarcoma (primary malignant).

• Wg. high risk of metastases and to reduce tumor mass before surgery (neoadjuvant chemotherapy).
• Followed by tumor extirpation; depending on the location of the tumor and the patient’s health, radiotherapy may be performed instead of surgery.
• Postoperatively takes place adjuvant chemotherapy

Therapy recommendations for osseous metastases (bone metastases; secondary malignant).

Surgical therapy of bone metastases (see under “Surgical therapy”) – palliative (without curative approach).

Radiotherapy

Bisphosphonates

Bisphosphonates – lead to inhibition of osteoclast-induced resorption of bone and enhance bone mineralization. This leads to a reduction in pain. Furthermore, they lead to a reduction in the pathological fracture risk. The following agents are available:

• Clodronate
• Ibandronate
• Pamidronate
• Zoledronic acid (synonym: zoledronate)

• Mode of action Bisphosphonates: inhibit osteoclasts (bone-degrading cells), leading to an increase in bone mass.
• Side effects: Bisphosphonate therapy is usually well tolerated, but occasionally arthralgia (joint pain), gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation, meteorism, esophagitis, hypocalcemia, osteonecrosis of the jaw (esp. a. Zoledronate) or even the “influenza-like” syndrome occurs.

Denosumab

Denosumab (monoclonal antibody that mimics the effects of osteoprotegerin (OPG) in bone metabolism) – used to prevent skeletal-related complications (SRE; pathologic fracture (“spontaneous fracture,” i.e., fracture of the bone during normal weight-bearing without an identifiable traumatic cause), radiation therapy to the bone, spinal cord compression (constriction of the spinal cord), or surgical procedures to the bone) in adults with bone metastases due to solid tumors.

• Mode of action Denosumab: antiresorptive by binding to RANK ligand → inhibition of osteoclast activity → decrease in bone resorption and increase in bone mass and strength.
• Contraindications:
  • Patients who have unhealed lesions from dental surgery or oral surgery.
  • A patient reminder card is introduced to increase patient awareness of the risk of osteonecrosis of the jaw and the precautions needed to minimize it.
  • Patients treated with denosumab must be given the patient reminder card with information about osteonecrosis of the jaw and the package insert.
• Side effects: Limb, muscle and skeletal pain, risk of osteonecrosis of the jaw and hypocalcemia.
• Caveat:
  • Osteonecrosis of the jaw bone and external auditory canal during therapy with bisphosphonates and denosumab.
  • In clinical trials in patients with advanced cancers, occurrence of increased incidence of new primary malignancies with denosumab compared with zoledronic acid.

Anti-hormonal therapy

Anti-hormonal therapy for hormone-sensitive primary tumors such as mammary carcinoma (breast cancer) or prostate carcinoma (prostate cancer) (for more information, see the diseases mentioned).