A continuation of the Sutent trial from Italy had the following (see below):
It was nice to see the high percentages of response - but of concern to me was the person who was responding for 17 months, then developed progressive disease. They stopped the Sutent, then the patient died 1 months later. I think it seems to be a dangerous time discontinuing anti-angiogenesis inhibitors and this is another case.
The other interesting mention in the abstracts was about a tubulin-liked drug (like Vinblastine). It really looks good - if it were closer to us and for kids, we would definitely try it - especially as there have been responders who have been on Vinblastine. The full abstract is below the Sutent one, but this is the interesting line: "one alveolar small part sarcoma patient, who had marked progression prior to enrollment, has received 21+ cycles of study drug with stable disease." I especially liked that the side effects seemed especially LOW.
It is put out by a little company though, so I do worry that it may take them a while to get to Phase II.
I also talked to Barbara Adam today about cryoablation. I'll add more general info for those who might consider that route.
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Abstract:
Background: ASPS is a rare soft tissue sarcoma, characterized by the t(X;17), resulting in the ASPL-TFE3 fusion protein. It carries a high metastatic potential with a typical indolent growth even in the advanced stages. ASPS is generally resistant to chemotherapy. We already reported on the activity of SM in 4 cases of ASPS. This series updates those results. Methods: Since July 2007, 10 patients (pts) with progressive metastatic ASPS (M/F 7/3; median age 24 yrs; site of primary: extremities 9, retroperitoneum 1; site of metastasis: lung 10, bone 3, liver 3, brain 2, other 4; pretreated pts:
have been treated with continuous SM 37.5 mg/day, on name-use basis. Responses were evaluated after 2 months from baseline, then every 3 months by CT scan and/or MRI, according to RECIST criteria. PET responses were evaluated in 5 cases. Biochemical analysis by phospho-RTK arrays complemented by downstream signaling pathway analysis was performed on 5 pts whose cryopreserved material was available. Results: At the time of the present analysis 8/10 pts are evaluable for response (2 just started), 8 pts are still on treatment. Treatment was fairly well tolerated (no G3-4 toxicity). After 3 months of treatment, 5 pts had RECIST PR, along with subjective improvement in symptoms, 1 SD, 2 PD. PR/SD were confirmed in all cases after 6 months. PET was consistent with response/progression. One patient had a secondary PD after 17 months of treatment and died one month later. Responses seemed to be long-lasting (>9 months in all cases), with one patient still responsive after 28 months. In 2 cases treatment interruptions lead to tumor progression. Response was re- established when restarting SM. Biochemical analysis showed good correlation between RTK activation profile and SM targets, and a uniform activation of AKT, ERK1-2, mTOR downstream pathways. Notably, a particularly strong activation of EGFR was evident in the case with SD. RET-mediated activation might be responsible of the 2 progressive cases. Conclusions: SM confirmed to be active in ASPS. Long- lasting dimensional responses were obtained. Interval disease progressions were recorded in case of treatment interruptions. Molecular analysis supported SM activity.Background: ALB 109564(a) [ALB] is a vinca alkaloid, which functions as a tubulin inhibitor, interfering with microtubule polymerization resulting in metaphase arrest. In preclinical studies, ALB was active in a wide variety of tumor types (e.g., colon, NSCLC, prostate) at concentrations comparable to those of approved vinca alkaloids. Methods: This study sought to determine the maximum tolerated dose based upon first cycle toxicity in 3-6 patients at each dose level, as well as to evaluate the pharmacokinetics of ALB when administered intravenously every three weeks. The starting dose was 1.2 mg/m2, and escalation proceeded according to a modified Fibonacci scheme. Results: 28 patients have been administered ALB across eight dose levels (1.2 to 12 mg/m2). No dose-limiting toxicities as well as no serious adverse events specifically attributed to ALB were observed. Through seven cohorts, adverse events reported to be at least possibly related to study drug were constipation (n=5), anemia (n=2), fatigue (n=2), blurred vision (n=1), decreased appetite (n=1), flushing (n=1), paresthesia (n=1), and rash (n=1); all were either grade 1 or 2. The overall half-life of ALB was 19.05 ± 8.80 hours, which is comparable to that of approved vinca alkaloids. Of 21 patients evaluable for clinical activity, one alveolar small part sarcoma patient, who had marked progression prior to enrollment, has received 21+ cycles of study drug with stable disease. An additional four patients have had stable disease after two or more cycles; one anal (7+ cycles), one pancreatic (5+ cycles), one colon (4 cycles), and one NSCLC (4 cycles). Conclusions: ALB is well tolerated and has shown preliminary activity in disease types not typically associated with approved vinca alkaloids. Further trials in soft tissue sarcoma are in development.