Oral malignant melanoma – the effect of coarse fractionation radiotherapy alone or with adjuvant carboplatin therapy

A retrospective study was undertaken of dogs presented to the Animal Health Trust for treatment of oral malignant melanoma, without radiographic evidence of pulmonary metastases. Group 1 (n = 13) received radiotherapy of the primary and any lymph node metastases (4 weekly fractions of 9 Gy); and group 2 (n = 15) were treated the same but additionally received between two and six doses carboplatin at 300 mg m^?2 every 3 weeks. Median survival times for the two groups were 307 and 286 days, respectively (P > 0.05). In addition, carboplatin therapy did not significantly reduce the proportion of dogs dying due to metastases (three from group 1 and four from group 2). We found no evidence of a beneficial effect of carboplatin therapy over radiotherapy alone.     

Results from the treatment of advanced stage squamous cell carcinoma of the nasal planum in cats, using a combination of intralesional carboplatin and superficial radiotherapy: a pilot study

Six cats with an advanced stage squamous cell carcinoma (SCC) of the nasal planum were treated with a combination of superficial radiotherapy and intralesional carboplatin therapy. This multimodality protocol was well tolerated by the majority of cats and resulted in complete responses in all cats (100%). Median follow‐up for all cats is 268 days, and the median time‐to‐recurrence, time‐to‐progression and overall survival have not yet been reached. Our study, although limited in number of animals and with a relatively short median follow‐up compared to other studies for this disease, suggests that a combination of radiotherapy and intralesional carboplatin is a useful treatment option for an advanced stage SCC of the nasal planum in cats and warrants further application of the multimodality approach presented here.     

Surgical excision of a feline orbital lacrimal gland adenocarcinoma with adjunctive cryotherapy and carboplatin‐impregnated bead implantation

The purpose of this report was to discuss the diagnosis, treatment, and outcome of a cat with an orbital lacrimal gland adenocarcinoma. A 14.5‐year‐old spayed female domestic shorthair cat was evaluated for a firm swelling at the left dorsotemporal orbital rim. The orbital mass was excised with preservation of the globe, and adjunctive cryotherapy was performed. A definitive diagnosis of lacrimal gland adenocarcinoma was obtained after histopathologic evaluation and histochemical staining with periodic acid–Schiff and mucicarmine. Thirteen months postoperatively, tumor regrowth occurred with a much larger osteolytic lesion, and a second surgery was performed consisting of tumor excision with implantation of carboplatin‐impregnated calcium sulfate hemihydrate beads. The cat has remained free of recurrence 11 months after the second surgery (26 months after initial diagnosis and surgery). A feline orbital lacrimal gland adenocarcinoma was successfully managed utilizing globe‐preserving surgical excision with adjunctive cryotherapy and subsequent carboplatin‐impregnated bead implantation. Orbital lacrimal gland adenocarcinoma in cats may not be as aggressive as other forms of periocular, head, and neck adenocarcinomas.     

Toxicity and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of canine appendicular osteosarcoma following limb amputation

Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.     

Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6‐week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re‐staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.     

Evaluation of intracavitary mitoxantrone and carboplatin for treatment of carcinomatosis,sarcomatosis and mesothelioma,with or without malignant effusions: A retrospective analysis of 12 cases (1997–2002)*

Carcinomatosis, sarcomatosis and mesothelioma, with or without malignant effusions, are difficult to treat and generally carry a poor prognosis. The purpose of this study was two‐fold; first, to determine the prognosis for dogs with carcinomatosis, sarcomatosis, or mesothelioma, with or without malignant effusions; second, to evaluate the safety and efficacy of treatment with intracavitary (IC) carboplatin and mitoxantrone in dogs with these syndromes. Nineteen dogs were evaluated. Seven were untreated and 12 were treated with IC chemotherapy (mitoxantrone and/or carboplatin), and multiple factors were analysed for significance with respect to survival time. The median survival time (MST) for untreated dogs was 25 days, whereas the MST for treated dogs was 332 days (Log Rank, P < 0.0001). Treatment with IC chemotherapy was well tolerated. This study suggests that IC chemotherapy with mitoxantrone and/or carboplatin is an effective treatment for dogs with carcinomatosis, sarcomatosis or mesothelioma, with or without malignant effusion.     

Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs

There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post‐operative management of ASAGAC. Seventy‐four dogs with naturally occurring ASAGAC underwent surgery. Forty‐four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC.     

Serum concentration and safety of intravenous drip versus subcutaneous administration of carboplatin in dogs

Carboplatin is used to treat certain cancers in dogs and cats and is routinely administered via intravenous drip (IVD). Subcutaneous (SC) administration has also been described. However, the toxicity, serum concentrations, and area under blood concentration-time curves (AUCs) of SC carboplatin are unknown. This study aimed to compare serum carboplatin concentrations in dogs after SC and IVD and to monitor any adverse events. In this crossover study, five dogs received SC or IV carboplatin (300 mg/m²). After a minimum of 3 weeks, each dog received the other treatment. No gross skin toxicity or abnormal clinical signs were observed in any of the dogs. Blood test abnormalities were detected in most dogs. Decreased neutrophil and platelet counts, and increased C-reactive protein (CRP) levels were found. There was no significant difference in the neutropenia, thrombocytopenia, and CRP scores between the groups. Systemic toxicities of SC carboplatin were comparable to those of IVD carboplatin. The time to maximum carboplatin concentration after SC was longer than that after IVD (P<0.001). SC carboplatin remained in the serum longer than IVD carboplatin (P=0.008). The AUC of SC was less than that of IVD (P=0.002). The AUC and time taken to reach the maximum concentration of SC carboplatin were lower than those of IVD carboplatin. This study suggests that SC carboplatin may be an efficacious option for the treatment of tumors in dogs, particularly where IVD administration is challenging.     

紫杉醇卡铂化疗联合放射治疗局部晚期非小细胞肺癌临床观察

目的：观察紫杉醇卡铂化疗联合放射治疗局部晚期非小细胞肺癌(NSCLC)的近期疗效及毒副反应。方法：32例局部晚期NSCLC患者，采用紫杉醇加卡铂联合化疗(紫杉醇135mg／m^2，静滴，第1天；卡铂300mg／m^2,静滴，第2天，每21天为l周期，共2—3周期)，并与放射治疗(常规分割，DT62—68Gy／3l一34次)交替进行(夹心疗法)。结果：全组CR2例，PRl6例，总有效率(CR PR)56．3％．无严重毒副反应。平均生存期14．5月。结论：紫杉醇卡铂化疗联合放射治疗局部晚期NSCLC能提高近期疗效，远处转移有降低趋势．且毒副作用可耐受，值得临床进一步观察研究。     

Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer‐bearing dogs

Rosiglitazone is an FDA‐approved peroxisome proliferator‐activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m² to seven dogs. Carboplatin was administered at 240–300 mg/m² in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose‐limiting toxicity was hepatic at a dose of 8 mg/m². Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ‐glutamyltranspeptidase values were noted.