Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double‐blind placebo‐controlled trial

Abstract Purpose: Updated results, including response rate data, from a randomized, double-blind, placebo-controlled study comparing thalidomide plus dexamethasone versus dexamethasone alone as primary therapy for newly diagnosed multiple myeloma (MM). Methods: Patients (pts) with previously untreated, symptomatic MM were eligible. Pts were randomized to Thal/Dex (Arm A) or placebo plus Dex (Arm B). Pts in Arm A received Thal 50 mg PO daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2; Dex 40 mg PO was given on days 1–4, 9–12, and 17–20. Pts in Arm B received placebo instead of Thal, and Dex as in Arm A. Each cycles was 28 days long. Treatment was continued until progression or undue toxicity. The primary endpoint was time to progression (TTP) defined using EBMT criteria. All analyses were conducted on an intent to treat basis. An independent data monitoring committee recommended release of results. Results: 470 pts were enrolled: 235 were randomized to Thal/Dex and 235 to placebo/Dex. Median follow up is 18 months. Median age was 65 yrs. The response rate (CR+PR) was significantly higher with Thal/Dex compared to placebo/Dex, 59% vs 42%, respectively, P<0.001. Eighty-two percent of patients have gone off-study. TTP was significantly superior with Thal/Dex vs placebo/Dex, median TTP not reached with Thal/Dex versus 8.1 months (95% CI: 6.5–12.8 months) with placebo/Dex, P<0.001. Major grade 3–4 events are summarized in the Table below. Deep vein thrombosis (DVT) was higher with Thal/Dex vs placebo/Dex, 15.4% vs 4.3%, respectively. Conclusions: Thal/Dex yields superior response rates and TTP compared to Dex alone when used as first-line therapy for multiple myeloma. Major Grade 3–4 adverse events Adverse Event Thal/Dex (n=234) Placebo/Dex (n=232) Venous thromboembolism (Grade >=3) 17.9% 4.3% Cerebral ischemia (Grade >=3) 3.0% 1.3% Myocardial ischemia (Grade >=3) 3.8% 2.2% Neuropathy (Grade >=3) 3.0% 0% Any toxicity (Grade >=4) 30.3% 22.8%

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Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Thalidomide Plus Dexamethasone Compared With Dexamethasone As Initial Therapy for Newly Diagnosed Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.1853 ◽

2008 ◽

Vol 26 (13) ◽

pp. 2171-2177 ◽

Cited By ~ 242

Author(s):

S. Vincent Rajkumar ◽

Laura Rosiñol ◽

Mohamad Hussein ◽

John Catalano ◽

Wieslaw Jedrzejczak ◽

...

Keyword(s):

Multiple Myeloma ◽

Controlled Trial ◽

Initial Therapy ◽

Controlled Study ◽

Primary Therapy ◽

Newly Diagnosed ◽

Time To Progression ◽

Double Blind ◽

Double Blind Placebo ◽

Long Term Impact

Purpose The long-term impact of thalidomide plus dexamethasone (thal/dex) as primary therapy for newly diagnosed multiple myeloma (MM) is unknown. The goal of this study was to compare thalidomide plus dexamethasone versus placebo plus dexamethasone (placebo/dex)as primary therapy for newly diagnosed MM. Patients and Methods In this double-blind, placebo-controlled trial, patients with untreated symptomatic MM were randomized to thal/dex (arm A) or to placebo plus dexamethasone (dex) (arm B). Patients in arm A received oral thalidomide 50 mg daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2 (28-day cycles). Oral dex 40 mg was administered on days 1 through 4, 9 through 12, and 17 through 20 during cycles 1 through 4 and on days 1 through 4 only from cycle 5 onwards. Patients in arm B received placebo and dex, administered as in arm A. The primary end point of the study was time to progression. This study is registered at http://ClinicalTrials.gov ( NCT00057564 ). Results A total of 470 patients were enrolled (235 randomly assigned to thal/dex and 235 to placebo/dex). The overall response rate was significantly higher with thal/dex compared with placebo/dex (63% v 46%), P < .001. Time to progression (TTP) was significantly longer with thal/dex compared with placebo/dex (median, 22.6 v 6.5 months, P < .001). Grade 4 adverse events were more frequent with thal/dex than with placebo/dex (30.3% v 22.8%). Conclusion Thal/dex results in significantly higher response rates and significantly prolongs TTP compared with dexamethasone alone in patients with newly diagnosed MM.

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Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.1997.1220903.x ◽

1997 ◽

Vol 27 (8) ◽

pp. 860-867 ◽

Cited By ~ 11

Author(s):

V.A. VARNEY ◽

J. EDWARDS ◽

K. TABBAH ◽

H. BREWSTER ◽

G. MAVROLEON ◽

...

Keyword(s):

Clinical Efficacy ◽

Specific Immunotherapy ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo

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A randomized double blind, placebo controlled trial of a Chinese herbal preparation (CH100) in chronic Hepatitis C

Gastroenterology ◽

10.1016/s0016-5085(01)81907-7 ◽

2001 ◽

Vol 120 (5) ◽

pp. A384-A384

Author(s):

L MOLLISON ◽

L TOTTEN ◽

C HOVELL ◽

K THAYNE ◽

C CONNELLY ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Controlled Trial ◽

Herbal Preparation ◽

Double Blind ◽

Double Blind Placebo ◽

Chinese Herbal

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Patients with non-cardiac chest pain (NCCP) recelving an empirical trial of high dose lansoprazole, demonstrate early symptom response. A double blind, placebo-controlled trial

Gastroenterology ◽

10.1016/s0016-5085(01)81101-x ◽

2001 ◽

Vol 120 (5) ◽

pp. A221-A221 ◽

Cited By ~ 6

Author(s):

R FASS ◽

G PULLIAM ◽

C HAYDEN

Keyword(s):

Chest Pain ◽

Controlled Trial ◽

High Dose ◽

Double Blind ◽

Early Symptom ◽

Double Blind Placebo ◽

Symptom Response

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40: Oral Ketoconazole for Prevention of Postoperative Penile Erection, a Prospective, Randomized, Double Blind, Placebo Controlled Trial

The Journal of Urology ◽

10.1016/s0022-5347(18)30305-7 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 14-15

Author(s):

Brian J. DeCastro ◽

Jack R. Walter ◽

Leah P. McMann ◽

Andrew C. Peterson

Keyword(s):

Penile Erection ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo

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992: Verapamil Versus Saline in Electromotive Drug Administration (EMDA) for Peyronie's Disease: A Double-Blind Placebo-Controlled Trial

The Journal of Urology ◽

10.1016/s0022-5347(18)33217-8 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 320-320

Author(s):

Jason M. Greenfield ◽

Sneha J. Shah ◽

Laurence A. Levine

Keyword(s):

Drug Administration ◽

Controlled Trial ◽

Peyronie’S Disease ◽

Double Blind ◽

Double Blind Placebo ◽

Peyronie's Disease ◽

Electromotive Drug Administration

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Effects of Mixed Dietary Supplements on Total Plasma Homocysteine Concentrations (tHcy): A Randomized, Double-Blind, Placebo-Controlled Trial

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000118 ◽

2012 ◽

Vol 82 (4) ◽

pp. 260-266 ◽

Cited By ~ 2

Author(s):

Salah E. Gariballa ◽

Sarah J. Forster ◽

Hilary J. Powers

Keyword(s):

Older Patients ◽

Controlled Trial ◽

Plasma Homocysteine ◽

Acute Illness ◽

Vitamin B ◽

Total Plasma ◽

Double Blind ◽

Double Blind Placebo ◽

Nutrient Supplement ◽

Plasma Thcy

Background: Although a number of studies have reported raised total plasma homocysteine (tHcy) concentrations in free-living older people, there are no data on homocysteine response to a mixed nutrient supplement in older patients. A raised plasma homocysteine concentration in older patients is partly a reflection of their co-morbidity, including impaired renal function, and there is uncertainty about the extent to which dietary interventions can improve plasma tHcy. Aim: To determine the plasma tHcy response to dietary supplements during acute illness. Methods: Two-hundred and thirty-six hospitalized, acutely ill older patients, who were part of a randomized double-blind placebo-controlled trial, were assigned to receive a daily oral nutritional supplement drink containing 1.3 mg of vitamin B2, 1.4 mg of vitamin B6, 1.5 μg of B12, 200 μg of folic acid, or a placebo, for 6 weeks. Outcome measures were plasma tHcy concentration at baseline, 6 weeks, and 6 months. Results: The mean plasma tHcy concentration fell among patients given the supplements (mean difference 4.1 µmol/L [95 % C.I, 0.14 to 8.03), p = 0.043], but tHcy concentration increased between 6 weeks and 6 months, after patients stopped taking the supplements [mean difference -2.0 µmol/L (95 % C.I, -03.9 to -0.18), p = 0.033]. About 46 % of patients in the placebo group and 55 % of patients in the supplement group had hyperhomocysteinemia (>14 µmol/L) at baseline compared with 45 % and 29 % at the end of the treatment period. Conclusions: A mixed nutrient supplement containing physiological amounts of B vitamins significantly reduced plasma tHcy concentrations in older patients recovering from acute illness.

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