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Evaluation of toxicities from combined metronomic and maximal-tolerated dose chemotherapy in dogs with osteosarcoma

J Small Anim Pract. 2014 Jul;55(7):369-74. doi: 10.1111/jsap.12228. Epub 2014 May 7.

Abstract

Objective: To evaluate the tolerability of a piroxicam and cyclophosphamide metronomic treatment protocol combined with carboplatin alone or carboplatin and doxorubicin at maximal-tolerated doses.

Methods: Retrospective study of 30 dogs diagnosed with osteosarcoma. All dogs underwent amputation and chemotherapy treatment with one of the two maximal-tolerated dose protocols. Metronomic chemotherapy was administered in conjunction with these protocols, and continued subsequently. The protocols included 0 · 3 mg/kg piroxicam and 10 to 12 mg/M(2) cyclophosphamide with 300 mg/M(2) carboplatin alone, or 300 mg/M(2) carboplatin alternating with 30 mg/M(2) doxorubicin.

Results: Fourteen dogs were treated with the carboplatin and metronomic protocol and 16 were treated with the carboplatin alternating with doxorubicin and metronomic protocol. Grades 3 and 4 toxicities overall were significantly (P = 0 · 018) more common in the former group. The disease-free interval of the carboplatin and metronomic group was 192 days, which was not significantly different (P = 0 · 916) to the 182 days for the carboplatin alternating with doxorubicin and metronomic group. The median survival times of the two groups were 217 and 189 days, respectively.

Clinical significance: Piroxicam and cyclophosphamide metronomic protocols can be safely administered in combination with maximal-tolerated dose chemotherapy protocols. A significantly higher frequency of toxicities was observed in dogs treated with the carboplatin and metronomic protocol.

MeSH terms

  • Administration, Metronomic / veterinary
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Agents, Alkylating / toxicity
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / veterinary*
  • Carboplatin / administration & dosage
  • Carboplatin / therapeutic use
  • Carboplatin / toxicity
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Cyclophosphamide / toxicity*
  • Dog Diseases / chemically induced
  • Dog Diseases / drug therapy*
  • Dogs
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity
  • Drug Therapy, Combination / veterinary
  • Female
  • Male
  • Osteosarcoma / drug therapy
  • Osteosarcoma / veterinary*
  • Piroxicam / administration & dosage
  • Piroxicam / therapeutic use
  • Piroxicam / toxicity*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Piroxicam
  • Doxorubicin
  • Cyclophosphamide
  • Carboplatin