Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.

1995 ◽  
Vol 13 (9) ◽  
pp. 2354-2360 ◽  
Author(s):  
G P Browman ◽  
D Bergsagel ◽  
D Sicheri ◽  
S O'Reilly ◽  
K S Wilson ◽  
...  

PURPOSE To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. PATIENTS AND METHODS In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. RESULTS Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. CONCLUSION Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.

1995 ◽  
Vol 13 (7) ◽  
pp. 1720-1725 ◽  
Author(s):  
A van der Gaast ◽  
J Verweij ◽  
A S Planting ◽  
W C Hop ◽  
G Stoter

PURPOSE We performed this study to identify prognostic factors in a subgroup of patients with carcinoma of unknown primary site treated with cisplatin combination chemotherapy. PATIENTS AND METHODS Seventy-nine patients with poorly differentiated adenocarcinoma or undifferentiated carcinoma of unknown primary site were treated on two consecutive phase II chemotherapy protocols. The first protocol consisted of treatment with 3-week courses of cisplatin, etoposide, and bleomycin (BEP). In the second protocol, cisplatin was administered weekly combined with oral administration of etoposide (DDP/VP). To identify prognostic factors, univariate and multivariate analyses were conducted. RESULTS In the univariate analysis, performance status, histology, liver or bone metastases, and serum levels of alkaline phosphatase and AST were significant variables to predict survival. In the multivariate analysis, performance status and alkaline phosphatase were the most important prognostic factors. CONCLUSION Good-prognosis patients had a performance score of 0 (World Health Organization [WHO]) and an alkaline phosphatase serum level less than 1.25 times the upper limit of normal (N). These patients had a median survival duration greater than 4 years. Intermediate-prognosis patients were characterized by either a WHO performance status < or = 1 or an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of 10 months and a 4-year survival rate of only 15%. The poor-prognosis group had both a WHO performance status > or = 1 and an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of only 4 months and none survived beyond 14 months. Treatment strategies for these three groups are discussed. It is suggested that this prognostic model be validated in other patients series.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4919-4919
Author(s):  
Lugui Qiu ◽  
Yu-jie Mai ◽  
Rei Li ◽  
Dehui Zou ◽  
Yafei Wang ◽  
...  

Abstract The clinical characteristics and treatment results of the multiple myeloma patients admitted to our hospital from January 1980 to December 2002 were retrospectively analyzed and compared in order to put forward a feasible therapeutic strategy for MM in China. Results: 1. Clinical characteristics (1) 432 cases with full follow-up statistics were analyzed. The median age was 57 years (20 to 80).The peak onset age were 50 to 60 years. The ratio of male to female was 2.35:1. (2) 81% patients had anemia(Hb<100 g/L) at diagnosis. The median proportion of tumor cells in the bone marrow was 0.38 (0.005–0.970). 72.1% with high β2-MG (>3mg/L), 60% of the patients had abnormities in X-rays. (3) M-protein peak was detected in 78.5% patients. IgG made up the majority in classification(48.1%), IgA (21.8%)and light-chain(20.5%)next to it. 144 patients were in stage IIIA(40%), and 87 cases in IIIB(24.1%)at first diagnosis. (4) The median survival duration was 27 months (1–137months). 2. Treatment results: 206 cases had integral therapeutic records in 432 patients. (1) 200 patients were administered with drugs therapy, and their 3-year and 5-year survival were 32.01% and 15.8% respectively. The OS, median survival, 3-year and 5-year survival in MP group(n=46) were 30.4%, 30 months, 21.96% and 13.2% respectively. 149 cases(72.3%)received multi-drug combined chemotherapy(CCT).The overall response was 50.3% and significant higher than that of MP group(P=0.01).While the median survival duration(30.5 months), 3-year and 5-year survival rates (35% and 16.7% respectively) were as same as MP group (P>0.05. (2). 38/200 cases (19%) were treated with interferon in combination with chemotherapy over 6 months. The overall response rates were 53.6%, and the median survival duration was 52 months, and presented an increased response(P=0.02)and a prolonged survival duration (P=0.0003) compared with the no interferon group(34.4%,27months respectively. (3)Thalidomide was administered to 29 cases(14.5%), including 5 who took it alone(2.5%). The overall response rates were 50.3%. (4) 6 patients received hematopoietic stem cell transplantation. 5 patients with autologous peripheral blood stem cell transplantation were alive averagely in 73±12.5 months by the end of the follow-up. Conclusion: 1) MM patients in China had poor prognostic characteristics except of younger age compared with the westerns, especially most patients were diagnosed at III phase with significant lower survival. 2) CCT yielded higher response rates but no longer duration of survival benefit than MP when used as treatment for MM. INF-a and Thalidomide could benefit MM by combination with chemotherapy. Among patients who are <60 years old with good performance, HSC could prolong survival duration.


2021 ◽  
Vol 1 (2) ◽  
pp. 35-42
Author(s):  
YURIKA NOGUCHI ◽  
NORIYOSHI IRIYAMA ◽  
HIROMICHI TAKAHASHI ◽  
YOSHIHITO UCHINO ◽  
MASARU NAKAGAWA ◽  
...  

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.


2003 ◽  
Vol 89 (2) ◽  
pp. 141-145 ◽  
Author(s):  
Aziz Karaoğrlu ◽  
Suayib Yalcin ◽  
Gülten Tekuzman ◽  
Ayse Kars ◽  
Ismail Çelik ◽  
...  

Aims and background We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. Methods A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. Results A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (≤45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. Conclusions We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.


1995 ◽  
Vol 13 (4) ◽  
pp. 910-913 ◽  
Author(s):  
N M Bleehen ◽  
E S Newlands ◽  
S M Lee ◽  
N Thatcher ◽  
P Selby ◽  
...  

PURPOSE Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies. PATIENTS AND METHODS Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course. Courses were repeated every 4 weeks and the dose was escalated to 200 mg/m2/d x 5 (total dose, 1 g/m2) after the first course if toxicity was acceptable. Patients were all chemotherapy-naive, except for two who had previously received interferon alfa and one who had received interleukin-2 (the latter patient had also received two phase I drugs some time previously). RESULTS A complete response (CR) was documented in three patients (all with lung metastases) and a partial response (PR) in nine patients (21% CR plus PR rate). Seven of 56 patients were not assessable for response because of early death or deterioration. The overall response rate excluding these patients is 12 of 49 (24%). The median response duration was 6 months (range, 2.5 to 22+). Toxicity of the regimen, which was mainly hematopoietic, was low. The median survival duration for all patients was 5.5 months (range, 0.5 to 29.5). For responders, the median survival duration was 14.5 months (range, 3 to 28+), with four patients still alive. CONCLUSION Temozolomide in the schedule used has as good activity in chemotherapy-naive metastatic melanoma as the other most active agents currently in use. Further studies of the drug on its own and in combination with other agents is recommended.


Cancer ◽  
2006 ◽  
Vol 106 (10) ◽  
pp. 2171-2180 ◽  
Author(s):  
Brett T. Brinker ◽  
Edmund K. Waller ◽  
Traci Leong ◽  
Leonard T. Heffner, Jr. ◽  
Istvan Redei ◽  
...  

1993 ◽  
Vol 11 (6) ◽  
pp. 1118-1123 ◽  
Author(s):  
A A Forastiere ◽  
M B Orringer ◽  
C Perez-Tamayo ◽  
S G Urba ◽  
M Zahurak

PURPOSE In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P &lt;0.00001), labeling index (0.25; &lt;0.0001), creatinine (0.23; &lt;0.0001), soluble IL6 receptor (0.3; &lt;0.0001), BM plasma cell percentage (0.16; &lt;0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P &lt; 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P &lt; 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P &lt; 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5487-5487
Author(s):  
Devendra K. Hiwase ◽  
Anthony P. Schwarer ◽  
Geraldine M. Bollard ◽  
Smita D. Hiwase ◽  
Michael Bailey

Abstract Aim: ASCT has improved survival in patients with multiple myeloma although most patients develop progressive disease. Absolute lymphocyte count recovery at day 15 (ALC-15) following ASCT has been reported as an independent prognostic indicator of overall survival (OS) and progression free survival (PFS) for patients with multiple myeloma. It is not only a good prognostic marker but may also have therapeutic significance. We evaluated absolute lymphocyte recovery on day 15 (ALC-15), day 30 (ALC-30), day 60 (ALC-60) as a prognostic marker following ASCT in patients with multiple myeloma. Method: Between 1992 and 2004, 119 consecutive patients underwent ASCT. ALC-15, ALC-30, ALC-60 were evaluated for impact on OS and PFS following ASCT. Information on known prognostic factors for multiple myeloma including age, BM plasma cells (PC), paraprotein (PP), international staging system (ISS staging) and disease response following stem cell transplant were also evaluated. Result: There were 119 (M/F, 79/43) patients and median age was 57 (30–70) years. Most patients (N=100) received melphalan 200 mg/m2 as conditioning chemotherapy. The median CD34 dose infused was 3.95 x 106/kg (1.30–33.7). Median ALC-15 was 190 (0–254) cells/ul, median ALC-30 was 1000 (60 to 5590) cells/ul and ALC-60 was 1290 (50–6570). There were 28% of patients in complete remission (CR) & 67% in partial remission (PR) following ASCT. On Multivariate analysis: ALC-30 was significantly associated with OS. Although there was higher PFS with higher lymphocyte count, the difference was not statistically significant. Other known prognostic factors such as ISS staging, PC at diagnosis, age at transplant and CR response following ASCT were also significantly correlated with OS & PFS. Survival analysis: Median OS was 64 (0.2 to 175) months and PFS 32 (1.7 to 175) months following PBSCT. In patients with ALC-30 &gt;500 cells/ul median OS was 80 months and 53 months in patients with ALC-30 &lt; 500 cells/ul (P= 0.0147). Fig 1: Overall survival following ASCT in months Fig 1:. Overall survival following ASCT in months PFS was 43 months in patients with ALC-30 &gt; 500 cells/ul and 31 months in patients with ALC-30 &lt; 500 cells/ul (P=0.39). Median ALC-30 was 1309 cells/ul in patients who were alive at last follow up while median ALC-30 was 879 cells/ul in patients who were deceased (P=0.0072) and in most of the patients (35/45, 77%) progressive disease was responsible for their demise. There was no significant correlation between CD34+ stem cells dose and lymphocyte dose in autograft with ALC-30 recovery (P=0.26). Conclusions: ALC-30 was an independent prognostic indicator of OS following ASCT in patients with multiple myeloma. There was trend for longer PFS in patients with ALC-30 &gt;500 cells/ul, although the difference was not statistically significant. This may be due small sample size and needs to be evaluated further in prospective study. We could not find a correlation between lymphocyte dose or CD34 dose in autograft with ALC-30 recovery. Lower ISS stage, less extensive marrow infiltration at diagnosis and complete response following PBSCT positively influences OS & PFS.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1670-1670
Author(s):  
Paul Mehan ◽  
Giridharan Ramsingh ◽  
Jingqin Luo ◽  
Daniel Morgansztern ◽  
Ravi Vij

Abstract Solitary plasmacytoma (PCM) is a focal, neoplastic, plasma cell disorder without evidence of systemic disease. While PCM is a clinically distinct entity, survival can be limited by progression to multiple myeloma. Prior studies have attempted to identify factors influencing survival in PCM but have been limited by small patient cohorts. This study identified 1472 patients with PCM using the SEER database between 1988 and 2004. The median age of the patients was 64 years (range 12–97), 65.4% male, 34.6% female, 83% Caucasians, 10.7% African Americans and 6.3% other races. 63.8% had medullary PCM and 36.2% extramedullary PCM. 84% of medullary PCM occurred in axial skeleton and the rest in appendicular skeleton. Extramedullary PCM most frequently occurred in the head and neck region (51.4%) followed by skin/subcutaneous tissue (16.2%), GI tract 6% and other sites (26.4%). 55.2% were treated with radiation therapy alone, 29.5% with radiation therapy and surgery and 15.3% with surgery alone. 558 died during this period and the mean overall survival was 6.83 years (range, 0–16.9). The cause of death was multiple myeloma in 49.6%, other cancers 20.9% and cardiovascular diseases 12.9%. In all patients, survival probability at one year was 87.6% (95% CI, 85–89%), at five years was 58.9% (95% CI, 56–62%), and at 10 years was 40.0% (95% CI, 36–44%). The five year overall survival in the ≤40yo cohort was 83.5% as compared to 76.7% and 44.8% in the 40–60yo and &gt;60yo groups, respectively (p&lt;0.0001). The five year disease specific survival probability in the ≤40yo cohort was 94.5% as compared to 86.0% and 66.2% in the 40–60yo group and &gt;60yo group, respectively (p&lt;0.0001) (figure 1)). Overall survival in the extramedullary PCM was 65.9% at five years as compared to 54.6% in the medullary PCM (p&lt;0.0001) and the disease specific survival in the extramedullary PCM was 86.2% compared to 70.1% in the medullary PCM (p&lt;0.0001) (figure 1). Multivariate analysis of disease specific survival revealed that younger age, male gender, extramedullary type, and race other than African American or Caucasian were favorable prognostic factors (Table 1). Younger age, extramedullary site, treatment with XRT + surgery, and race other than African Americans were associated with improved overall survival by multivariate analysis (Table 1). To our knowledge, this is the largest published review of survival in PCM. This study identifies several prognostic risk factors influencing survival in PCM. These risk factors can be used to identify patients at high risk for progression to multiple myeloma. Those at highest risk could be considered for future trials comparing adjuvant systemic therapy compared to local therapy alone. Table 1. Multivariate Analysis of Prognostic Factors Disease Specific Survival Overall Survival Variable Category HR 95% CI P HR 95%CI P Abbreviations: HR, Hazard Ratio; Q, Confidence Inverval Sex Female --- -- --- -- --- --- Male 0.74 0.58~ 0.94 0.01 0.95 0.80~1.13 0.57 Age &lt;40yo --- --- --- --- --- --- 40–60yo 2.68 115~ 6.2 0.02 1.74 1.04~2.91 0.03 &gt;60yo 6.94 3.06~ 15.73 &lt;0.01 5.55 3.40~9.06 &lt;0.01 Race Black --- --- --- --- --- --- White 0.74 0.52~ 1.06 0.1 0.72 0.56~0.92 0.01 Others 0.31 0.13~ 0.75 &lt;0.01 0.48 0.29~0.79 &lt;0.01 Primary Site Extramedullary --- --- --- --- --- --- Medullary 2.35 1.74~.3.18 &lt;0.01 1.37 1.13~1.65 &lt;0.01 Treatment Surgery Only --- --- --- --- --- --- XRT Only 0.90 0.62~ 1.31 0.59 0.82 0.64~1.04 0.10 XRT + Surgery 0.84 0.55~1.26 0.39 0.68 0.52~0.89 &lt;0.01 Period 1988–1993 --- --- --- --- --- --- 1994–1999 0.96 0.72~1.30 0.8 0.96 0.78~1.19 0.74 2000–2004 0.94 0.68~1.30 0.7 0.94 0.75~1.18 0.6 Figure 1: Figure 1:.


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