The taxanes (including paclitaxel and docetaxel) represent a class of chemotherapy drugs that interfere with microtubule function leading to altered mitosis and cellular apoptosis . Paclitaxel is rarely used in the treatment of STS because it demonstrates limited efficacy . The main reason for the limited efficacy of paclitaxel is probably that there is a practical limitation to the delivered dose due to high toxicity [10, 20, 21, 22]. The toxicity of docetaxel-based chemotherapy is greater than that of doxorubicin-based chemotherapy. Thus, although the clinical efficacy of the two regimens is similar, docetaxel-based chemotherapy is considered as a second line regimen for the treatment of advanced STS .
Treatment with paclitaxel or docetaxel is associated with a number of clinical problems, including poor drug solubility, allergic reactions, serious dose limiting toxicities . These clinical problems are related to the solvents used to dilute these anticancer drugs: Cremophor EL for paclitaxel and polysorbate 80 for docetaxel . To solve these problems, nab-paclitaxel was developed to be free of the conventional solvents used in the injections. The newly nab-paclitaxel is prepared by encapsulating paclitaxel in albumin nanoparticle . The nab-paclitaxel can pass through the leaky capillary junctions in the tumor bed more easily than through the normal vessels in healthy tissue, and is thus taken up selectively by tumor tissues and cells. According to clinical data, nab-paclitaxel offers several improvements over conventional, solvent- and Cremophor-based paclitaxel, including lower toxicities, shorter administration time, higher efficacy, and the lack of a need for premedication . Several previous studies have demonstrated that nab-paclitaxel has greater efficacy and a more favorable safety profile (compared with solvent-based paclitaxel) in many malignancies [13, 24, 25].
To our knowledge, this study is the first to investigate the safety and effectiveness of nab-paclitaxel/ gemcitabine combination chemotherapy in advanced STS patients. In this retrospective observational study, we observed that nab-paclitaxel was effective for the treatment of STS, with an ORR of 41.2%, and a median-PFS of six months. Considering that all of these patients received nab-paclitaxel/ gemcitabine treatment following failed doxorubicin-based chemotherapy, the effectiveness of nab-paclitaxel/ gemcitabine chemotherapy is increased compared to doxorubicin-based chemotherapy and docetaxel/ gemcitabine combination therapy reported by other studies [2, 4]. The toxicity of nab-paclitaxel/ gemcitabine is also lower than that of doxorubicin and docetaxel/ gemcitabine . In addition, the results of this study demonstrate that the effectiveness of nab-paclitaxel/ gemcitabine is significantly greater than that of conventional paclitaxel and docetaxel in some subtypes of STS, such as epithelioid sarcoma. Previous studies have demonstrated the limited efficacy of conventional paclitaxel and docetaxel in the treatment of epithelioid sarcoma [26, 27]. In the present study, three of the five epithelioid sarcoma patients achieved PR, and one patient achieved SD.
The results of our study indicate that nab-paclitaxel is more effective and has lower toxicity than conventional paclitaxel or docetaxel in STS. In view of the fact that nab-paclitaxel is superior to conventional paclitaxel in the treatment of many malignant tumors [13, 24, 25], nab-paclitaxel should not simply be considered as a drug with similar properties to paclitaxel. It should be regarded as a new chemotherapeutic drug; and the efficacy of this drug should be evaluated in various malignancies. For example, though paclitaxel is considered to be ineffective in the treatment of osteosarcoma , it should not be assumed that treatment of osteosarcoma with nab-paclitaxel is also ineffective. Indeed, we speculate that treatment of osteosarcoma with nab-paclitaxel may yield promising results.
This study provides preliminarily results demonstrating the safety and effectiveness of nab-paclitaxel/ gemcitabine in STS treatment. Although this study has some limitations, including the small sample size, retrospective design and the lack of a control group, we can still conclude that nab-paclitaxel/ gemcitabine combination chemotherapy used in STS treatment demonstrates promising effectiveness with low toxicity, and is worthy of further study. In view of the low toxicity and convenience of nab-paclitaxel, we believe that the combination of nab-paclitaxel and other anticancer drugs (chemotherapeutic drugs, TKIs, PD-1 inhibitors) in the treatment of STS may produce significant results. In elderly sarcoma patients, where effective treatment is wanting due to poor tolerance , nab-paclitaxel may be of significant benefit. Fortunately, several clinical trials on the efficacy of nab-paclitaxel in sarcomas are currently recruiting patients (Table 5). To further investigate the efficacy of nab-paclitaxel in STS, a randomized clinical trial will be conducting soon (ChiCTR2000030250).