Cancer Treatment

Followup of resected gastric cancer

Patients with early gastric cancer have an excellent prognosis after appropriate treatment, with a high survival rate and a low rate of recurrence.There are no guidelines as to how to follow gastric cancer. A recent review concluded: " Early detection of asymptomatic gastric cancer recurrence did not improve overall survival of patients with recurrence after curative resection. Until development of more effective treatment for this disease, close follow-up may offer no survival benefit. " After 5 years, it is usually assumed that a cancer is cured and the proposed intensive re-evalaution in not supported by credible literature.It is still unclear whether intensive follow-up after surgery produces significant benefits in patients with gastric cancer. A previous retrospective study concluded that follow-ups were not useful.There have been no data to suggest that chemotherapeutic agents are useful in the treatment of recurrent gastric cancer detected during follow-up.

C. Kunisaki, H. Akiyama, M. Nomura, G. Matsuda, Y. Otsuka, H. Ono, Y. Nagahori, H. Hosoi, M. Takahashi, F. Kito, et al.
Significance of Long-Term Follow-Up of Early Gastric Cancer
Ann. Surg. Oncol., March 1, 2006; 13(3): 363 - 369.

Yasuhiro Kodera, MD, Seiji Ito, MD, Yoshitaka Yamamura, MD, Yoshinari Mochizuki, MD, Michitaka Fujiwara, MD, Kenji Hibi, MD, Katsuki Ito, MD, Seiji Akiyama, MD and Akimasa Nakao, Follow-Up Surveillance for Recurrence After Curative Gastric Cancer Surgery Lacks Survival Benefit Annals of Surgical Oncology 10:898-902 (2003)

Kodera Y, Ito S, Yamamura Y, et al. A follow-up surveillance for recurrence after curative gastric cancer surgery lacks survival benefit. Ann Surg Oncol 2003; 10:898–902.[

Cyclosporin for ITP

There are patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, WinRHO, Rituxan, IVGG, and splenectomy. Cyclosporin is useful for some patients who occasionally respond to it. There are many published case reports of its effectiveness. It is recommended for refractory cases in standard reviews.

Since very few pateints are this refractory, prospective studies are not possible but cyclosporine is widely accepted, including being mentioned in compenida for off-label use for Evan's syndrome which is a combination of immune thrombocytopenia and hemolytic anemia.

D B. Cines and J. B. Bussel
How I treat idiopathic thrombocytopenic purpura (ITP)
Blood, October 1, 2005; 106(7): 2244 - 2251.

Kappers-Klunne MC, van't Veer MB. Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenia purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001;114: 121-125

Bourgeois E, Caulier MT, Delarozee C, et al. Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis. Br J Haematol. 2003;120:1079-1088

Leukine for melanoma

Lay Summary: Leukine is being explored for treating melanoma.

Leukine (granulocyte macrophage colony stimulating factor, GM-CSF, Sargramostim), which is approved for marketing for hematopoietic reconstitution and reversal of iatrogenic neutropenia, also has activity as a macrophage activator. It has been reported that Leukine stimulates peripheral blood monocytes in vitro to become cytotoxic for human melanoma cells. It has further been shown in clinical trials that in vivo administration of Leukine at low doses also results in monocyte activation as shown by enhanced cytotoxicity. Finally, Leukine causes release of an angiogenesis inhibitor by the macrophages. Becasue of these effects, interest was aroused in its use for melanoma.

A trial of therapy in the adjuvant setting was favourable. The median survival was prolonged over three-fold in patients who received Leukine to 34.3 months compared to matched historical controls (median survival 10.2 months). The observed 2-year survival was 64% in the study patients vs. 15% in the controls, (p < 0.001). Toxicity was minimal, the major side effect being mild fatigue; there were no reports of Grade 4 toxicity or serious adverse events.

An interim analysis of another trial was presented at the 6th International Conference on Admuvant Therapy of Melanoma in Stockholm in 2006 and 5th International Conference on Adjuvant Therapy of Melanoma in Athens in March, 2004. It supports the results of the earlier trial and suggests that Leukine improves survival in this patient population. In addition, one of the cooperative study groups, the Eastern Cooperative Oncology Group, has initiated a Phase III prospective randomized trial to further evaluate this therapy (E4697). Accrual of 800 patients has ben completed, but many patients are still undergoing treatment and results of this study will not be known for several years. Finally, there is a trial to gather additional information about efficacy of this treatment and to determine the immunologic effects of GM-CSF in patients with melanoma.

The therapy is being currently investigated and is clearly experimental/investigational. The only adjuvant therapy approved at this time is interferon.

For metastatic setting, it is even more experimental, since immune mechanisma may not work for metastatic disease. A trial in this setting as well is referenced.

Spitler, LE, Grossbard, ML, Ernstoff MS, et al:  Adjuvant therapy of Stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol 18:1614-1621, 2000

http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=100307

nccn.org, melanoma