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

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. &ldquo;The rate of serious side effects was low with CAPTEM. We had no hospitalizations or treatment-related deaths,&rdquo; Fine said. The most common Grade 3/4 toxicities were lymphopenia (35%), hyperglycemia (6%), thrombocytopenia (3%), and diarrhea (3%).

Fine and the study&rsquo;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).

&ldquo;In this study we&rsquo;re seeing patients who had been given 6 months to live that are still alive 8 years after starting CAPTEM,&rdquo; Fine said. &ldquo;The regimen was effective even in patients with tumors that hadn&rsquo;t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation or surgery.&rdquo;

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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