Background: The Will Rogers phenomenon occurs when newer technology allows for more sensitive detection of tumor spread, resulting in stage migration and an apparent improvement in patient survival. We investigated whether use of highly sensitive positron emission tomography (PET) scanning in non-small cell lung cancer has had this effect. Methods:We performed a retrospective analysis involving 12 395 patients with non-small cell lung cancer in the pre- PET (1994PET ( -1998 and PET (1999PET ( -2004 periods. Interperiod differences in staging procedures, clinical variables, and patient survival were evaluated.Results: There was a 5.4% decline in the number of patients with stage III disease and an 8.4% increase in the
SummaryThis phase II study evaluated the safety and efficacy of lenalidomide in combination with rituximab in patients with relapsed/refractory, indolent non-Hodgkin lymphoma (NHL). Patients were treated with daily lenalidomide in 28-d cycles and weekly rituximab for 4 weeks. Lenalidomide was continued until progression or unacceptable toxicity. Twenty-two patients were assessed for FCGR3A polymorphisms. Thirty patients were enrolled; 27 were evaluable for response. The overall response rate (ORR) was 74% including 44% complete responses (CR); median progression-free survival (PFS) was 12Á4 months. The 13 rituximab refractory patients had an ORR of 61Á5% (four CR/unconfirmed CR). The ORR was 77% in the 22 follicular lymphoma patients (nine CR/unconfirmed CR). At a median follow-up time of 43 months, the median duration of response and time to next therapy were 15Á4 and 37Á4 months, respectively. Most common grade 3/4 adverse events were lymphopenia (45%), neutropenia (55%), fatigue (23%) and hyponatraemia (9%). The ORR and PFS in patients with low-affinity FCGR3A polymorphisms (F/F and F/V) suggest that lenalidomide may improve the activity of rituximab in these patients. These data suggest that combining lenalidomide with rituximab can produce durable responses with acceptable toxicity in patients with indolent NHL.
An objective causality assessment suggests that quetiapine was the highly probable cause of TTP in this patient. Early recognition, discontinuation of the drug, and institution of plasmapheresis are paramount for prompt resolution of this life-threatening hematologic disorder.
BACKGROUNDOverexpression of the HER‐2/neu oncoprotein has been reported to occur in ≤ 60% of patients with prostate carcinoma and to correlate with shortened survival. Trastuzumab is a humanized monoclonal antibody to the HER‐2 receptor and has activity against HER‐2–positive breast carcinoma, more so when combined with a taxane. The authors screened for HER‐2 overexpression in patients developing hormone‐refractory prostate carcinoma (HRPC) and conducted a Phase II trial of trastuzumab plus docetaxel in HER‐2–positive patients.METHODSParaffin‐embedded tumor specimens from potentially eligible patients were screened for HER‐2 expression by immunohistochemistry (IHC) and/or amplification by fluorescent in situ hybridization (FISH). Shed HER‐2 was also assessed by enzyme‐linked immunoradsorbent assay (ELISA). Patients with HER‐2–positive tumor specimens (IHC 2+ or 3+ or FISH ratio > 2) were initially randomized to receive either single‐agent trastuzumab or docetaxel. After two treatment cycles, nonresponding patients received the trastuzumab/docetaxel combination. Treatment was comprised of 30 mg/m2 of docetaxel weekly for 6 weeks followed by a 2‐week break and 4 mg/kg of trastuzumab intravenously during Week 1 then 2 mg/kg per week thereafter. The cycle length was 8 weeks.RESULTSOne hundred patients with HPRC were screened. IHC results were as follows: 3+ (n = 1), 2+ (n = 6), 1+ (n = 26), 0 (n = 39), and insufficient tissue specimen/not tested (n = 28). Only 3 of 37 patients had elevated shed HER‐2 by ELISA (> 15 mg/mL). None overexpressed HER‐2 by IHC. FISH amplification was found in 0 of 34 tissue samples. Of seven patients with IHC 3+ or 2+, four were tested by ELISA and two by FISH. None were abnormal. Age and Gleason score did not correlate with IHC status. Of the seven patients eligible for the Phase II study, only four agreed to participate. The trial was thus closed for nonfeasibility (the overall HER‐2 positivity rate was < 20%). No patient responded to trastuzumab alone. The median survival was not reached and the median progression‐free survival was 7 months.CONCLUSIONSHER‐2 overexpression by IHC in archival prostate carcinoma specimens was infrequent. There was no apparent correlation among IHC, ELISA, and FISH, although the sample size was limited. Conclusions regarding the predictive value of HER‐2 status on outcome after trastuzumab‐based therapy were not reached and were only drawn after larger‐scale screening efforts. The authors estimated that 1000 patients need to be screened to complete accrual to a 40‐patient efficacy trial. Cancer 2004. © 2004 American Cancer Society.
1679 Poster Board I-705 Background Lenalidomide (Revlimid®) is a potent immunomodulatory agent that has recently demonstrated clinical activity in the treatment of relapsed/refractory Multiple Myeloma and low- and int-1 risk Myelodysplastic syndromes with the del (5q) mutation. Laboratory data has shown that lenalidomide enhances T- and NK-cell mediated immune synapse formation and ADCC, and it exerts antiproliferative activity. In relapsed/refractory (R/R) NHL lenalidomide treatment achieved modest responses, although duration of response was >16.5 months (Witzig et al JCO, in press). Synergistic activity between lenalidomide and rituximab has been reported in lymphoma cell and animal models. Here we assess safety and efficacy of the lenalidomide and rituximab combination (R2) in patients with R/R indolent NHL. Methods Eligible patients had relapsed/refractory indolent NHL with measurable disease, ≥1 prior therapy, and ECOG PS 0-2. Oral lenalidomide was administered once daily on days 1-21 of a 28-day cycle, and was continued until disease progression. Rituximab 375mg/m2 IV was initiated on day 15 of cycle 1, and repeated weekly for a total of 4 doses; if after cycle 2 patient had less than a complete response (CR), 4 additional doses could be administered at discretion of the treating physician. After Gr. 3 tumor lysis syndrome (TLS) developed in 2 of the first 4 patients, the protocol was amended to reduce lenalidomide starting dose from 25 mg to 20mg daily, and TLS prophylaxis was provided with allopurinol in subsequently enrolled patients. Response and progression were evaluated according to IWG criteria (Cheson et al 1999). Results Of 15 patients currently enrolled on study, 14 received >2 cycles of R2, and 12 are evaluable for response. Median age for evaluable patients is 60 yrs (range: 50-91), 5 pts are female, and histologies include FL (n=9), SLL (n=1), and marginal zone lymphoma (n=2). Median time from diagnosis to treatment on study was 7.5 years (3.3-19), median number of prior therapies was 4 (range:1-11), and 9 patients were considered heavily pretreated (defined as ≥ 3 prior courses of therapy). All patients received prior rituximab, 6 patients had rituximab-resistant disease (defined as no response or relapse ' 6 months after initiating rituximab), and 5 patients had received prior radioimmunotherapy. Of 12 evaluable patients, 10 (83.3%) responded to R2, including 5 patients (41%) with a CR and 4 patients (33%) with a PR. Responses occurred in 4 of 6 patients (66%) with rituximab refractory disease, and in 7 of 9 (77%) heavily pretreated patients. Of 9 patients with R/R FL, 5 (55%) achieved a CR and 3 (33%) had a PR in response to R2, for an 88% ORR. At a median follow-up of 12 months, the median progression free survival has not been reached. Most common grade 3/4 adverse events were fatigue (2/12, 16%), neutropenia (3/12, 25%), lymphopenia (4/12, 33%), and hyponatremia (2/12, 16%). After prophylaxis was initiated, TLS was not observed at the 20 mg dose level. Conclusion This is the first study to demonstrate that the R2 combination is generally well tolerated and active in patients with R/R indolent NHL. Clinical activity was particularly noted among patients with R/R FL, who achieved 88% OR and 55% CR rate. The tolerability profile of R2 was consistent with other studies of each agent individually in the R/R setting. TLS prophylaxis and monitoring is recommended, particularly during initial cycles of treatment. These data support further evaluation of the potential clinical synergy between rituximab and lenalidomide in larger studies of FL and in earlier lines of therapy. Disclosures Off Label Use: Lenalidomide for treatment of non-hodgkin's lymphoma. Tuscano:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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