Sustained partial response of an intra-abdominal desmoid tumor treated with gemcitabine,5-fluorouracil and leucovorin
Authors: M.A. Wright, B. Schuler, E. Szabo, J.L. Grem
Journal: Annals of Oncology (2003)

We report a 66-year-old male with a history of intra-abdominal desmoid tumor, who experienced a sustained partial response to therapy while participating in an Institutional Review Board-approved phase I clinical trial of weekly gemcitabine, infusional 5-fluorouracil (5-FU) and leucovorin. The patient originally presented in 1993 with lower back pain and was found to have an intra-abdominal desmoid tumor, which was completely resected. Two years later, an abdominal recurrence was completely resected; he received adjuvant therapy with sulindac and vitamin C for 1 year. A subsequent tumor recurrence was deemed unresectable and he received tamoxifen for a total period of 24 months before disease progression. He was then treated with vinblastine and methotrexate for nine cycles. Upon disease progression, he was referred for participation in our protocol in July 1999.Upon enrollment, he was asymptomatic and had normal laboratory test results. A computed tomography (CT) scan was remarkable for a homogeneously enhancing mass in the left lower quadrant, which measured 14.5 × 9 cm (product 132 cm2; Figure 1A). Gemcitabine 1080 mg/m2 was administered as a30 min infusion on days 2 and 9 of each 3-week cycle. Leucovorin 20 mg/m2 was given orally on days 1 and 8 and by i.v. push on days 2 and 9, followed by a 24-h infusion of 5-FU 2250 mg/m2 on days 2 and 9. Due to minimal toxicity, the gemcitabine dose was increased to 1300 mg/m2 at the start of cycle 4. The patient requested to change to a 2 weeks on, 2 weeks off schedule after cycle nine. Restaging studies performed every three cycles showed gradual shrinkage of the tumor. The tumor met the criteria for a partial response in May 2000 (9 × 6 cm; product 54 cm2) and the response was confirmed 4 weeks later: 9 × 5.5 cm. A restaging scan performed in August 2002 showed continued shrinkageto 5.5 × 3.0 cm (product 16.5 cm2), which represents an 88% decrease in the tumor area over a 37.3 month interval (Figure 1B). By the time of writing, the patient had received 42 cycles of therapy with minimal toxicity, except for grade 1–2 fatigue.Intra-abdominal desmoid tumors are usually locally invasive, frequently recur after major surgery, and often cannot be completely resected due to encasement of vital structures [1.Anthony T. Rodriguez-Bigas M.A. Weber T.K. Petrelli N.J. Desmoid tumors.J Am Coll Surg. 1996; 182: 369-377PubMed Google Scholar, 2.Biermann J.S. Desmoid tumors.Curr Treat Options Oncol. 2000; 1: 262-266Crossref PubMed Scopus (34) Google Scholar]. Initiation of cytotoxic chemotherapy has usually been reserved for patients whose disease cannot be resected and has progressed despite a trial of non-cytotoxic medical therapies, such as hormonal therapy or non-steroidal anti-inflammatory agents [3.Waddell W.R. Gerner R.E. Indomethacin and ascorbate inhibit desmoid tumors.J Surg Oncol. 1980; 15: 85-90Crossref PubMed Scopus (121) Google Scholar, 4.Klein W.A. Miller H.H. Anderson M. DeCosse J.J. The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis.Cancer. 1987; 60: 2863-2868Crossref PubMed Scopus (147) Google Scholar, 5.Wilcken N. Tattersall M.H. Endocrine therapy for desmoid tumors.Cancer. 1991; 68: 1384-1388Crossref PubMed Scopus (217) Google Scholar]. Our patient developed recurrent or progressive disease after sulindac, tamoxifen and combination chemotherapy. There have been no prospective clinical trials evaluating the results of chemotherapy in the treatment of intra-abdominal desmoid tumor. Published case reports and case series have utilized various combination chemotherapy regimens involving two or three drugs such as doxorubicin, dactinomycin, vincristine or vinblastine, cyclophosphamide or ifosfamide, dacarbazine, carboplatin and methotrexate [6.Poritz L.S. Blackstein M. Berk T. et al.Extended follow-up of patients treated with cytotoxic chemotherapy for intra-abdominal desmoid tumors.Dis Colon Rectum. 2001; 44: 1268-1273Crossref PubMed Scopus (54) Google Scholar, 7.Skapek S.X. Hawk B.J. Hoffer F.A. et al.Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children.J Clin Oncol. 1998; 16: 3021-3027Crossref PubMed Scopus (118) Google Scholar]. To our knowledge, our patient is the first reported example of a sustained partial response using gemcitabine–5-FU in the therapy of intra-abdominal desmoid tumor. We report a 66-year-old male with a history of intra-abdominal desmoid tumor, who experienced a sustained partial response to therapy while participating in an Institutional Review Board-approved phase I clinical trial of weekly gemcitabine, infusional 5-fluorouracil (5-FU) and leucovorin. The patient originally presented in 1993 with lower back pain and was found to have an intra-abdominal desmoid tumor, which was completely resected. Two years later, an abdominal recurrence was completely resected; he received adjuvant therapy with sulindac and vitamin C for 1 year. A subsequent tumor recurrence was deemed unresectable and he received tamoxifen for a total period of 24 months before disease progression. He was then treated with vinblastine and methotrexate for nine cycles. Upon disease progression, he was referred for participation in our protocol in July 1999. Upon enrollment, he was asymptomatic and had normal laboratory test results. A computed tomography (CT) scan was remarkable for a homogeneously enhancing mass in the left lower quadrant, which measured 14.5 × 9 cm (product 132 cm2; Figure 1A). Gemcitabine 1080 mg/m2 was administered as a30 min infusion on days 2 and 9 of each 3-week cycle. Leucovorin 20 mg/m2 was given orally on days 1 and 8 and by i.v. push on days 2 and 9, followed by a 24-h infusion of 5-FU 2250 mg/m2 on days 2 and 9. Due to minimal toxicity, the gemcitabine dose was increased to 1300 mg/m2 at the start of cycle 4. The patient requested to change to a 2 weeks on, 2 weeks off schedule after cycle nine. Restaging studies performed every three cycles showed gradual shrinkage of the tumor. The tumor met the criteria for a partial response in May 2000 (9 × 6 cm; product 54 cm2) and the response was confirmed 4 weeks later: 9 × 5.5 cm. A restaging scan performed in August 2002 showed continued shrinkageto 5.5 × 3.0 cm (product 16.5 cm2), which represents an 88% decrease in the tumor area over a 37.3 month interval (Figure 1B). By the time of writing, the patient had received 42 cycles of therapy with minimal toxicity, except for grade 1–2 fatigue. Intra-abdominal desmoid tumors are usually locally invasive, frequently recur after major surgery, and often cannot be completely resected due to encasement of vital structures [1.Anthony T. Rodriguez-Bigas M.A. Weber T.K. Petrelli N.J. Desmoid tumors.J Am Coll Surg. 1996; 182: 369-377PubMed Google Scholar, 2.Biermann J.S. Desmoid tumors.Curr Treat Options Oncol. 2000; 1: 262-266Crossref PubMed Scopus (34) Google Scholar]. Initiation of cytotoxic chemotherapy has usually been reserved for patients whose disease cannot be resected and has progressed despite a trial of non-cytotoxic medical therapies, such as hormonal therapy or non-steroidal anti-inflammatory agents [3.Waddell W.R. Gerner R.E. Indomethacin and ascorbate inhibit desmoid tumors.J Surg Oncol. 1980; 15: 85-90Crossref PubMed Scopus (121) Google Scholar, 4.Klein W.A. Miller H.H. Anderson M. DeCosse J.J. The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis.Cancer. 1987; 60: 2863-2868Crossref PubMed Scopus (147) Google Scholar, 5.Wilcken N. Tattersall M.H. Endocrine therapy for desmoid tumors.Cancer. 1991; 68: 1384-1388Crossref PubMed Scopus (217) Google Scholar]. Our patient developed recurrent or progressive disease after sulindac, tamoxifen and combination chemotherapy. There have been no prospective clinical trials evaluating the results of chemotherapy in the treatment of intra-abdominal desmoid tumor. Published case reports and case series have utilized various combination chemotherapy regimens involving two or three drugs such as doxorubicin, dactinomycin, vincristine or vinblastine, cyclophosphamide or ifosfamide, dacarbazine, carboplatin and methotrexate [6.Poritz L.S. Blackstein M. Berk T. et al.Extended follow-up of patients treated with cytotoxic chemotherapy for intra-abdominal desmoid tumors.Dis Colon Rectum. 2001; 44: 1268-1273Crossref PubMed Scopus (54) Google Scholar, 7.Skapek S.X. Hawk B.J. Hoffer F.A. et al.Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children.J Clin Oncol. 1998; 16: 3021-3027Crossref PubMed Scopus (118) Google Scholar]. To our knowledge, our patient is the first reported example of a sustained partial response using gemcitabine–5-FU in the therapy of intra-abdominal desmoid tumor.