Patient assessment and feasibility of treatment in older patients with cancer: results from the IN-GHO® Registry.

PURPOSE: Predicting feasibility of treatment in older patients with cancer is a major clinical task. The Initiative Geriatrische Hämatologie und Onkologie (IN-GHO®) registry prospectively collected data on the comprehensive geriatric assessment (CGA), physician's and patient's-self assessment of fitness for treatment, and the course of treatment in patients within a treatment decision aged ≥ 70 years. PATIENTS AND METHODS: The registry included 3169 patients from 93 centres and evaluated clinical course and treatment outcomes 2-3 and 6 months after initial assessment. Fitness for treatment was classified as fit, compromised and frail according to results of a CGA, and in addition by an experienced physician's and by patient's itself. Feasibility of treatment (termed IN-GHO®-FIT) was defined as a composite endpoint, including willingness to undergo the same treatment again in retrospect, no modification or unplanned termination of treatment, and no early mortality (within 90 days). RESULTS: CGA classified 30.0% as fit, 35.8% as compromised, and 34.2% as frail. Physician's and patient's-self assessment classified 61.8%/52.3% as fit, 34.2%/42.4% as compromised, and 3.9%/5.3%, as frail, respectively. Survival status at day 180 was available in 2072 patients, of which 625 (30.2%) had died. After 2-3 months, feasibility of treatment could be assessed in 1984 patients. 62.8% fulfilled IN-GHO®-FIT criteria. Multivariable analysis identified physician's assessment as the single most important item regarding feasibility of treatment. CONCLUSION: Geriatricians were involved in 2% of patients only. Classification of fitness for treatment by CGA, and physician's or patient's-self assessment showed marked discrepancies. For the prediction of feasibility of treatment no single item was superior to physician's assessment. However CGA was not performed by trained geriatricians.

Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study.

OBJECTIVE: Multiple myeloma remains incurable and retreatment with available therapies is of substantial interest. METHODS: This retrospective observational study included data from 35 patients treated initially and at the first relapse with bortezomib-containing regimens. RESULTS: Bortezomib retreatment provided a similar depth and time to response as first-line therapy; however, as could be expected, the duration of response was shorter with retreatment. The tolerability profile was similar with bortezomib as the first- and second-line therapy, with no evidence of cumulative toxicity. CONCLUSION: These findings support bortezomib retreatment after a treatment-free interval of ≥6 months in patients who achieved at least a partial response to the first-line bortezomib-based therapy.

Prospective, randomized, controlled, and open study in primarily inoperable, stage III non-small cell lung cancer (NSCLC) patients given sequential radiochemotherapy with or without epoetin alfa.

BACKGROUND AND PURPOSE: Induction chemotherapy is associated with anemia in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy. This randomized, open-label study compared the effect of sequential radiochemotherapy (RCHT) versus RCHT + epoetin alfa (RCHT + EPO), with respect to 2-year overall survival (OS). MATERIAL AND METHODS: Patients ⩾18 years received sequential RCHT; one arm also received EPO (chemotherapy day 1, when Hb<12 g/dL). Kaplan-Meier analysis with log-rank test, and Cox-regression methods were performed. RESULTS: Of the 385 patients randomized (RCHT + EPO: n = 195; RCHT: n = 190), 78 (RCTH + EPO: 46 [23.6%]; RCHT: 32 [16.8%]) were anemic at baseline. Two-year OS was higher in RCHT + EPO-treated versus RCHT-treated (28.5% [95% CI: 22.2-35.1%] versus 20.6% [95% CI: 15.1-26.8%] [p = 0.2278]), and requirement for RBC transfusion was lower (24/195 [12.3%] versus 61/190 [32.1%]). In anemic (baseline) patients (post hoc analysis), median survival was shorter in RCTH-treated (212 days) versus RCHT + EPO-treated (343 days) (Hazard ratio = 1.62 [95% CI: 0.99-2.63], p = 0.0525). Adverse events were documented in 72.7% (RCHT + EPO: 75.0%; RCHT: 70.5%) patients, and thrombovascular events (TVEs) in 45 patients (RCHT + EPO: 16.7%; RCHT: 7.9%; p = 0.0099). CONCLUSIONS: A statistically non-significant trend for 2-year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline anemia, although this trend was not maintained in the overall population with inoperable NSCLC.

Phase II study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma.

This phase II study is the first prospective evaluation of bortezomib-dexamethasone as second-line therapy for relapsed/refractory multiple myeloma. A total of 163 patients were enrolled to receive four cycles of bortezomib-dexamethasone. Patients were investigator-assessed for response at cycle 5 Day 1, then treated as follows: responding patients received another four cycles of bortezomib-dexamethasone, while patients with stable disease were subsequently randomized to sequential treatment with a further four cycles of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide. The primary end point was response to sequential therapy; however, this could not be evaluated because investigator-assessed response rates to bortezomib-dexamethasone after four cycles were high, and an insufficient number of patients were randomized to sequential treatment per protocol. Among all 163 patients, validated best confirmed response rate was 66%, including 37% complete/very good partial responses; median response duration was 9.7 months. After a median follow up of 16.9 months, median time to progression and progression-free survival were 9.5 and 8.6 months, respectively; estimated 1-year overall survival was 81%. Median glomerular filtration rate improved from baseline during treatment. Among 58 patients with baseline glomerular filtration rate below 50 mL/min, 24 had renal responses. Grade 3/4 adverse events included: thrombocytopenia (17%), anemia (10%), constipation (6%), peripheral sensory neuropathy (5%), and polyneuropathy (5%). Overall, 57% of neuropathy events improved/resolved; median time to improvement was 2.1 months. These findings suggest bortezomib-dexamethasone represents an active, feasible second-line treatment option for patients with relapsed/refractory myeloma.

A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma.

Multiple myeloma (MM) typically follows a relapsing course with many patients requiring multiple therapies. This single-arm phase 2 study prospectively evaluated the efficacy and safety of bortezomib retreatment in MM patients who had relapsed after achieving at least a partial response (≥ PR) to prior bortezomib-based therapy. Patients aged ≥ 18 years, with measurable, secretory MM, who relapsed ≥ 6 months after prior bortezomib treatment were eligible. Patients received up to eight cycles of bortezomib (± dexamethasone). The primary endpoint was best confirmed response at retreatment; secondary endpoints included duration of response (DOR), time to progression (TTP), and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. A total of 130 patients (median of two prior lines of therapy) were enrolled and received retreatment. At retreatment, 28% and 72% of patients received bortezomib and bortezomib-dexamethasone, respectively. Overall response rate was 40%. In patients who achieved ≥ PR, median DOR and TTP were 6.5 and 8.4 months, respectively. Thrombocytopenia was the most common grade ≥ 3 AE (35%). Forty percent of patients experienced neuropathy events, which improved and resolved in a median of 1.5 and 8.9 months, respectively. In conclusion, bortezomib retreatment was effective and tolerable in relapsed MM patients, with no evidence of cumulative toxicities.

Increased hemoglobin levels and improved quality-of-life assessments during epoetin alfa treatment in anemic cancer patients: results of a prospective, multicenter German trial.

This prospective, open-label, multicenter study was undertaken to determine the safety and efficacy of epoetin alfa in increasing hemoglobin levels and improving quality of life (QOL), specifically fatigue, in cancer patients receiving chemotherapy with or without radiotherapy (n=702). Epoetin alfa, 10,000 IU three times a week s.c. for 8-18 weeks, increased the mean hemoglobin level relative to baseline (1.0 +/- 1.5 g/dl by week 4 and > or =1.7 g/dl from week 10 through the end of the trial), with 63.4% of patients experiencing > or =2 g/dl increases in hemoglobin above baseline at some time during the study. Fatigue is an important component of QOL. Physicians, nurses, and patients independently assessed patient fatigue level on a linear-analogue scale. Although all three groups reported improvements in patient fatigue over the course of the study (p <.0001), the magnitude of fatigue ratings and their relationship to tumor response and to hemoglobin level varied by group. Overall, epoetin alfa was well tolerated and effective in improving hemoglobin levels and decreasing fatigue in patients undergoing chemotherapy.