Capecitabine/ Temozolomide Elicits 'Extraordinary' Responses in Chemo-Resistant NETs

January 15, 2014

Patients with carcinoid and pituitary NETs, who have been traditionally chemo-resistant, may obtain "extraordinary responses" with capecitabine and temozolomide (CAPTEM), according to data from an interim analysis of an ongoing phase II study.

Robert Lance Fine, MD

Patients with carcinoid and pituitary NETs, who have been traditionally chemo-resistant, may obtain "extraordinary responses" with capecitabine and temozolomide (CAPTEM), according to data from an interim analysis of an ongoing phase II study. Robert Lance Fine, MD, reported these data at a presscast prior to the 2014 Gastrointestinal Cancers Symposium.

In the pituitary group, “There were two of the three patients who were end-stage disease on respirators because of spinal-cord compression from their tumor. They both had complete responses, got off-machine, and now are still free of tumor, close to 4 years out now and on continual treatment,” said Fine, lead study author and an associate professor of Medicine at New York Presbyterian Hospital-Columbia University Medical Center.

CAPTEM demonstrated tumor sh­­rinkage in 43% of patients in the study, all with progressive, moderately, and well-differentiated metastatic NETs (N=28), and the combination therapy stalled tumor growth in 54% of these patients. CAPTEM either stalled disease progression or shrank tumors in 95% of patients whose disease worsened after standard high-dose octreotide, according to the ASCO written statement. Median progression-free survival (mPFS) was 30 months.

Notably, 41% of patients with carcinoid tumors (n=12) experienced tumor shrinkage. Response rate (RR) to chemotherapy for these patients is generally 0-4%, according to Fine.

Among the four patients with pituitary tumors resistant to radiation therapy, chemotherapy, and surgery, two had complete remissions (CR) with CAPTEM, one had a 75% reduction in tumor size, and one has had stable disease (SD) for 5 years.

The primary objective of the study is RR based upon RECIST, and secondary objectives include PFS, overall survival (OS; from time of initiation of therapy), and toxicity evaluation. Inclusion criteria were: age <80; ECOG performance status (PS) 0-2; adequate hematologic, renal, and liver function; and failure on high-dose octreotide.

Various subtypes of metastatic NETs were treated as part of the study (See Table).

Table. CAPTEM Interim Study Results

# of Subjects

% SD

% PR

% CR

% PD

PFS

OS

Carcinoid(typical and atypical)

12

58

33

8

0

>23.9

>31.5

Pituitary

3

0

33

67

0

>41.6

>41.6

Pancreatic NET

11

55

36

0

9

>20.0

>24.4

Medullary Thyroid

2

100

0

0

0

>22.8

>27.7

Overall

28

54

32

11

3

>22.2

>29.1

PD=progressive disease; PR=partial response

Most patients experienced only mild side effects. “The rate of serious side effects was low with CAPTEM. We had no hospitalizations or treatment-related deaths,” Fine said. The most common Grade 3/4 toxicities were lymphopenia (35%), hyperglycemia (6%), thrombocytopenia (3%), and diarrhea (3%).

Fine and the study’s co-authors believe that CAPTEM may eventually replace all other second-line therapies for advanced neuroendocrine tumors, ASCO said in a written statement.

Fine and colleagues are working on other CAPTEM studies that they hope will make the therapy even more effective (eg, combining CAPTEM with drugs that block the platelet-derived growth factor [PDGF] pathway).

“In this study we’re seeing patients who had been given 6 months to live that are still alive 8 years after starting CAPTEM,” Fine said. “The regimen was effective even in patients with tumors that hadn’t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation or surgery.”

Fine RL, Gulati AP, Tsushima D, et al. Prospective phase II study of capecitabine and temozolomide (CAPTEM) for progressive, moderately, and well-differentiated metastatic neuroendocrine tumors. Presented at: 2014 Gastrointestinal Cancers Symposium (Presscast);January 14, 2014. Abstract 179.

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