F. A. Greco

Cancer of Unknown Primary Site

The so-called CUP syndrome (cancer of unknown primary) is defined as one or more histologically proven metastases of a malignant tumor for which the localization cannot be determined in spite of intensive diagnostic measures [1].

Phase II trial of rituximab and short duration chemotherapy followed by 90Y-ibritumomab tiuxetan as first-line treatment for patients with follicular lymphoma: A Minnie Pearl Cancer Research Network phase II trial

6519 Background: First-line treatment with combination chemotherapy + rituximab improves molecular complete remission (CR) rates and lengthens remission duration in patients (pts) with follicular NHL. In a previous phase II trial, we demonstrated a high CR rate with short course chemotherapy + rituximab (CHOP-R or CVP-R). In an attempt to further improve the CR rate, we added 90Y-ibritumomab tiuxetan (Zevalin) after CHOP-R.nnnMETHODSnPreviously untreated pts with follicular lymphoma (grades 1-3) and stages II-IV were eligible. Additional entry criteria: ECOG PS 0-2; adequate organ function; no CNS involvement; no HIV infection; informed consent. Pts with cardiac ejection fraction < 45% received CVP instead of CHOP. All pts first received 4-weeks of rituximab (375mg/m2 weekly x 4), then 3 courses of CHOP-R (standard doses). After complete restaging, responding pts with bone marrow involvement < 25% received 90Y-ibritumomab tiuxetan 5 weeks after the last dose of CHOP-R. Final restaging was performed 12 weeks after 90Y-ibritumomab tiuxetan.nnnRESULTSn33 of 40 pts have been accrued, with median follow-up of 10 months. Pt characteristics: median age, 56 years; stage IV, 54%; M/F = 16/17. Prior to 90Y-ibritumomab tiuxetan, 27 of 28 pts (96%) had objective response (9 CR). All pts completing CHOP-R were eligible for 90Y-ibritumomab tiuxetan. 22 pts have completed therapy and been restaged: 19 pts (86%) are in CR, with 3 PRs. 10 pts with PR converted to CR after 90Y-ibritumomab tiuxetan. No unexpected toxicity was seen during CHOP-R therapy. Hematologic toxicity following 90Y-ibritumomab tiuxetan: gr 4 neutropenia 18%; gr 4 thrombocytopenia 0; RBC transfusion 5%; platelet transfusion 18%; neutropenia/fever 5%; GI bleed 5%. 90Y-ibritumomab tiuxetan caused no grade 3/4 nonhematologic toxicities.nnnCONCLUSIONSnFirst-line CHOP-R followed by 90Y-ibritumomab tiuxetan is highly active and well tolerated in pts with follicular NHL. Further follow-up is necessary to determine progression-free and overall survival, and to monitor for late toxicity. [Table: see text].

Paclitaxel with mitoxantrone, fluorouracil, and high-dose leucovorin in the treatment of metastatic breast cancer: a phase II trial.

PURPOSEnPaclitaxel is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. In this phase II study, we added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin (NFL).nnnPATIENTS AND METHODSnForty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous (i.v.) infusion on day 1, mitoxantrone 10 mg/m2 by i.v. bolus on day 1, 5-FU 350 mg2/m by i.v. bolus on days 1, 2, and 3, and leucovorin 300 mg i.v. over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients.nnnRESULTSnTwenty-three of 45 assessable patients (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. Hospitalization for treatment of fever during neutropenia was required in 13% of courses, and two patients died as a result of sepsis. Two patients developed severe congestive heart failure after a large cumulative anthracycline dose.nnnCONCLUSIONnThis combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than anticipated based on previous results with the NFL regimen or with paclitaxel administered at this dose and schedule as a single agent. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with the paclitaxel/doxorubicin combination.

Weekly bolus topotecan as first-line therapy for extensive stage small cell lung cancer in patients who are elderly, poor performance status, or have severe coexistent illness: A Minnie Pearl Cancer Research Network phase II trial

7275 Background: Topotecan given intravenously for 5 consecutive days every 3 weeks is standard second-line therapy for patients (pts) with relapsed small cell lung cancer (SCLC) and ovarian cancer. Weekly bolus topotecan produces significantly less toxicity than the 5 day schedule, and appears as active as the standard schedule in pts with relapsed ovarian cancer.nnnMETHODSnThis ongoing phase II study was designed to evaluate the toxicity and response rate of weekly bolus topotecan in pts with previously untreated extensive stage SCLC who were elderly (> 65 years), poor performance status (PS), or had severe coexistent medical illness. Topotecan 4mg/m2 IV over 30 minutes for 12 consecutive weeks was planned. Dose modifications were made based on toxicity. Pts were evaluated for response after 4 weeks; at least 3 weekly treatments were required to be evaluable.nnnRESULTSnSeventeen pts of the required 40 pts have thus far been enrolled; 12 men, 5 women, ages 64-81 (median 71); PS 0=1, 1=4, 2=12). Thirteen pts are evaluable for response. Two pts have had partial responses (15%); 6 pts stable tumor (45%). Grade 3/4 neutropenia has been seen in 4 of 17 pts (24%), but no grade 3/4 thrombocytopenia was observed. Grade 2 fatigue was observed in 10 pts (56%) and grade 3 fatigue in 6 pts (35%). A total of 107 weeks of therapy have been administered. There were 15 weeks of treatment delay and 8% required dose reductions.nnnCONCLUSIONSnWeekly bolus topotecan appears to have modest activity and is well tolerated in this poor prognostic group of pts with previously untreated extensive stage SCLC. We expect to evaluate 15 additional pts soon. Severe myelosuppression is seen less often than expected compared to the standard 5 day schedule of topotecan. Fatigue is an important toxicity and may be reduced by planned rest weeks. Studies of weekly topotecan in combination with other active cytotoxic agents should be considered in pts with extensive stage SCLC. [Table: see text].