{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:46:14Z","timestamp":1790077574434,"version":"4.0.1"},"reference-count":22,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:p> PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. <\/jats:p><jats:p> PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg\/m<jats:sup>2<\/jats:sup>. Fludarabine 20 mg\/m<jats:sup>2<\/jats:sup> was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. <\/jats:p><jats:p> RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II\/III dose (cyclophosphamide 1,000 mg\/m<jats:sup>2<\/jats:sup>), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. <\/jats:p><jats:p> CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg\/m<jats:sup>2<\/jats:sup> day 1 and fludarabine 20 mg\/m<jats:sup>2<\/jats:sup> days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients. <\/jats:p>","DOI":"10.1200\/jco.2000.18.5.987","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T07:10:51Z","timestamp":1487920251000},"page":"987-987","source":"Crossref","is-referenced-by-count":67,"title":["Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up\u2014A Report From the Eastern Cooperative Oncology Group"],"prefix":"10.1200","volume":"18","author":[{"given":"Howard S.","family":"Hochster","sequence":"first","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Oken","sequence":"additional","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane N.","family":"Winter","sequence":"additional","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo I.","family":"Gordon","sequence":"additional","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce G.","family":"Raphael","sequence":"additional","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Cassileth","sequence":"additional","affiliation":[{"name":"From the New York UniversityNew York, NY; Virginia Piper Cancer Institute, Minneapolis, MN; Northwestern University, Chicago, IL; University of Rochester Cancer Center, Rochester, NY; and University of Miami, Miami, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R2-0149","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1985.3.6.769"},{"key":"R3-0149","unstructured":"Peterson  BA,  Frizzera  JR,  Anderson  JR, et al:  Response of low grade lymphoma to cyclophosphamide or cyclophosphamide, Adriamycin, vincristine, prednisone and bleomycin.  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