{'fraction_non_alphanumeric': 0.033544452263664086, 'fraction_numerical': 0.02674173117522871, 'mean_word_length': 4.9971870604782, 'pattern_counts': {'":': 0, '<': 4, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Learning management better to help kill two birds with one stone

This issue of the Asia Pacific Journal of Clinical Oncology contains a full report of a review article of using SU11248 (sunitinib), an inhibitor of the vascular endothelial growth factor (VEGF) tyrosine kinase in the treatment of metastatic renal cell carcinoma (RCC) as well as gastrointestinal stromal tumor (GIST). With sunitinib rapidly moving toward full US Food and Drug Administration review and with an Expanded Access Program, this drug has been ready for use by patients and their oncologists for some time. Recently, the Food and Drug Administration approved sunitinib (Sutent, Pfizer) for the treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib (Gleevec, Novartis). Sunitinib was also granted accelerated approval for the treatment of metastatic renal cell carcinoma (MRCC). This is the first time that the agency has approved an oncology drug for the treatment of two indications simultaneously. Sunitinib is an oral tyrosine kinase inhibitor targeting predominantly the vascular endothelial growth factor (VEGFR) and platelet-derived growth factor (PDGFR) receptors. Of greatest interest for the clinician is the observation of tumor shrinkages as well as the median time to tumour progression (TTP) and progression-free survival (PFS) among the enrolled refractory solid tumor patients. This has already led to a number of phase II and phase III studies in GI stromal tumor as well as in renal cell cancer patients. A double-blind clinical trial conducted in 56 centers in Asia, Europe, and North America, enrolling 312 adults with GIST, randomized 2 : 1 to either oral sunitinib (50 mg) or placebo once daily for 4 weeks followed by 2 weeks off schedule. Sunitinib significantly increased the median TTP, to 27.3 weeks, versus 6.4 weeks for placebo (P < 0.0001). It also resulted in superior PFS (24.1 weeks, vs 6.0 weeks; P < 0.0001). The objective response rate for sunitinibtreated patients was 6.8 versus 0% for those on placebo (P = 0.006). An international phase III trial of previously untreated patients (n = 750) with metastatic RCC were randomized to receive either 6-week cycles of sunitinib (50 mg po once daily for 4 weeks, followed by 2 weeks off) or IFN-a (9 MU sc three times weekly). Sunitinib was associated with a higher objective response rate than IFN-a (31 vs 6%, P < 0.001). Use of sunitinib showed more than double progression-free survival (PFS) when compared with IFN-a, (11 vs 5 months, P < 0.001). As a result, sunitinib would almost certainly enter the standard therapeutic armamentarium. Given that sunitinib is only one of several effective broadspectrum kinase inhibitors preferentially targeting VEGFR and PDGFR in clinical practice. The merit of this article is the emphasis of the management of adverse events, although the article reports that sunitinib is reasonably well tolerated, with asthenia, hypertension, dermatitis, and mild myelosuppression as the major toxicities. There is also the rare incidence of hypothyroidism which appears to increase with the duration of sunitinib therapy in GIST patients, with 18, 29 and 90% of patients developing hypothyroidism after 36, 52 and 96 weeks respectively. Abnormal serum thyroid stimulating hormone (TSH) values have been documented in 62% of patients receiving sunitinib. Generally, as might be expected, changing the class of targets aimed at DNA division and cellular proliferation to those that are aimed at the intracellular signaling and angiogenesis might also change the toxicity profiles to ones that most oncologists must be get used to in the near future. Hypertension, for example, was one of the most common toxicities observed in the study. Importantly, this may contribute to some of the rare cardiovascular toxicities. As has been seen with the epidermal growth factor receptor inhibitors such as Iressa and Tarceva, skin toxicities were also common but rarely serious. The lesson for clinicians is that antihypertensive and skin care regimens must be learned and a new standardized toxicity criteria may need to be developed Asia–Pacific Journal of Clinical Oncology 2007; 3: 165–166 doi:10.1111/j.1743-7563.2007.00112.x