Thalidomide + Interferon for Metastatic Renal Cell Cancer: Abstracts and Commentary
This annotated bibliography is part of CancerGuide, a web page created by Steve Dunn, a patient, and is part of my review of Thalidomide for the Treatment of Kidney Cancer. My conclusion from these data is that adding interferon to thalidomide does not improve the results of treatment and may well make it more toxic.
Phase II Trial Of Thalidomide And Interferon-Alpha In Advanced Renal Cell Carcinoma
Kevin P Ridenhour, Dennis Kubinski Diana Stindt M. C Hall Suzanne E Patton Frank M Torti
Proc Am Soc Clin Oncol. [Meeting Abstract] 2002;Abstract 2429
Comprehensive Cancer Center of Wake Forest Univ, Winston-Salem, NC.
Introduction: We report herein the interim results of thalidomide combined with interferon-alpha, both of which have anti-angiogenic properties, in advanced renal cell carcinoma.
Methods: 37 patients with metastatic renal cell carcinoma are to be enrolled with a planned interim analysis after 17 evaluable patients. Interferon-Alpha (Roferon, Roche Labs) was administered at 5 mu sq t.i.w. Thalidomide (Thalomid, Celgene Corp.) was initiated at 100 mg p.o. qhs for 2 wks. The dose of thalidomide was then further escalated by 200 mg q 2 wks to a maximum dose of 1000 mg or grade 3 or 4 toxicities encountered. Patients were assessed with a CT of the C/A/P, bone scan, CXR and, if indicated, brain MRI. After 12 wks of therapy, the patients were reassessed.
Results: The median age was 62 years. Performance status was 0 – 2. Measurable disease sites at entry: kidney (14 pts.), lung (17 pts.), adrenal gland (5 pts.), skeletal structures (9 pts.), retroperitoneal nodes (7 pts.), liver (2 pts.) and peritoneum (1 pts.). 25 pts. have been enrolled in this study (6 are not yet evaluable). Within 4 wks of initiation, 1 pt. died of disease complications at 3 wks, 1 was taken off study due to the appearance of a brain metastasis at 1 wk of therapy, and 2 were taken off study due to grade 4 fatigue and somnolence. The remaining 15 pts. received 4 or more weeks of treatment. Of these, 3 pts. were taken off study: 1 developed grade 4 fatigue at 5 wks., 1 developed disease progression with new pleural effusions and pulmonary metastasis at 8 wks, and 1 developed CHF at 9 weeks. 2 pts. were taken off thalidomide due to grade 4 somnolence and rash, but continued on interferon. Of the 12 pts. who have completed 12 wks of therapy, no CR or PR have been observed. However, 7 demonstrated SD.
Conclusion: A number of patients who had progressive disease upon study entry stabilized. Further accrual is ongoing. Pharmacokinetic analysis is also underway to evaluate any correlation between plasma thalidomide levels and response or toxicity.
This study had no partial or complete remissions in 19 evaluable patients, but there were 7 patients with stable disease after 12 weeks of treatment. This is generally similar to results of the studies with thalidomide alone, some of which had a few partial responses, and others of which had only stable disease. I can see no hint here that adding interferon is making things better.
A Phase II Study Investigating The Use Of Thalidomide In Conjunction With Interferon-A In Patients With Metastatic Renal Cell Carcinoma
Paul D. Nathan, Dana Walker Helen Bridle Paul Ross Anna Stevenson Siow M. Lee Tim G. Eisen Martin E. Gore.
Proc Am Soc Clin Oncol. [Meeting Abstract] 2001;Abstract 1058
Royal Marsden Hospital, London, UK; North Middlesex Hospital, London, UK; Middlesex Hospital, London, UK.
We intended to recruit 20 patients to a phase II study examining the toxicity of combination IFN-[alpha] and thalidomide treatment. Due to concerns regarding the toxicity of treatment the study was closed after accrual of 13 patients. Patients were established on 9mu IFN-[alpha] (Roferon) sc 3x weekly after a single introductory dose of 4.5mu. Two weeks later thalidomide was introduced at a starting dose of 100mg nocte and was dose escalated monthly in 100mg increments to a maximum dose of 400mg. Baseline clinical assessment, routine blood tests, serum for biological markers and quality of life questionnaires were obtained and repeated at each monthly visit. Tumour measurements were performed at baseline and 3 monthly. Nine male and four female patients with metastatic RCC were entered onto the study (average age = 56). 1/13 patients had been previously treated with immunotherapy. 10/13 were ECOG performance status 0-1, 3/13 were PS = 2. No responses to treatment were seen. Four patients experienced visual disturbances. One of these patients experienced complex partial seizures and another experienced transient numbness in his right arm and loss of speech. Of the other two patients experiencing visual disturbances one reported peri-oral tingling, facial numbness and a left sided headache and the other significant depression. CT scans excluded cerebro- vascular events or malignancy in all four. The maximum dose of thalidomide reached was 300 mg in the patient experiencing seizures and 200mg in the other three patients. One other patient experienced a Stevens-Johnson reaction to combination IFN-[alpha] and thalidomide treatment (200mg) which resolved on withdrawal of study drugs and treatment with steroids. In conclusion, we report significant toxicity of combination treatment with IFN-[alpha] and thalidomide at this dosing schedule. Neurological toxicity was greater than would be expected with either drug alone, particularly the incidence of visual disturbance and epileptiform symptoms. EEG results and biomarker studies will be presented.
This study closed early because of unexpectedly severe side effects. If the treatment were effective, the benefits could be worth cost in side effects. Unfortunately, not only was there a distressingly high rate of neurological side effects, but there was no sign this treatment worked.
Unexpected Toxicity Of Combination Thalidomide And Interferon Alpha-2a Treatment In Metastatic Renal Cell Carcinoma.
Nathan, P. D.; Gore, M. E., and Eisen, T. G.
J Clin Oncol. 2002;Mar 1; 20(5):1429-30.
This is from the same doctors as the previous reference. I haven’t got the paper and I don’t have an abstract, but I think the title alone says a lot about what’s going on here!