You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within in the paragraph. Each drug combination should be assigned to one of the following three categories:

- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.
- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.
- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.

Please format your answer as a json array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.

As an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:

[["artesunate", "artemether", "COMB"], ["Nifedipine", "Labetalol", "Prazosin", "POS"]]

The paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.

In your output, return only the json array and no other text. If no drug combinations appear, return an empty array `[]`.

paragraph: A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naïve castration-resistant prostate cancer. To investigate the efficacy and safety of combining vandetanib, an orally available multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR), with bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). ### methods This was an open-label, randomized phase II multi-center study. Eligible patients had rising PSA on androgen deprivation therapy, minimal symptoms and were chemotherapy-naïve. Protocol therapy was either vandetanib 300 mg oral daily plus bicalutamide 50 mg oral daily (Arm A) or bicalutamide 50 mg oral daily alone (Arm B) with cross-over to vandetanib monotherapy at progression. The primary endpoint was PSA response (≥ 50 % decline from baseline). ### results Thirty-nine patients were recruited, 19 in Arm A and 20 in Arm B. PSA response was comparable in Arm A and Arm B (18 vs. 19 %). Time to PSA progression was 3.16 months (95 % confidence interval (CI): 1.09, not reached (NR)) for Arm A and 3.09 months (95 % CI: 1.22, NR) for Arm B. Treatment discontinuation due to adverse events was more common in Arm A compared to Arm B (42 vs. 5 %; p = 0.019). Treatment with vandetanib was associated with a reduction in soluble VEGFR-2 levels after two cycles but an increase in plasma VEGF levels. ### conclusion The combination of vandetanib and bicalutamide was associated with considerable toxicity and did not have superior efficacy over bicalutamide alone . Further evaluation of this combination is not warranted in mCRPC.

sentence: The combination of vandetanib and bicalutamide was associated with considerable toxicity and did not have superior efficacy over bicalutamide alone .
[["vandetanib", "bicalutamide", "NEG"]]