The association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy

BACKGROUND:

In men with metastatic castration‐resistant prostate cancer (CRPC), the association of measurable tumor responses with overall survival (OS) is unknown. The authors retrospectively evaluated the TAX327 phase 3 trial to study this relation.

METHODS:

Eligible patients for this analysis included those with World Health Organization (WHO)‐defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated by using the Kaplan‐Meier method, and the prognostic relation of WHO‐defined radiologic response with OS was performed by using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and at 2, 3, 4, and 6 months after baseline.

RESULTS:

Four hundred twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty‐seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD, 24%) and 160 (38.8%) did not have a after‐baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months) or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. The authors found a significant association between ≥30% prostate‐specific antigen (PSA) declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD, and 34.4% with PD. Radiologic response remained a significant but modest post‐treatment prognostic factor for OS after adjusting for treatment, pain response, and ≥30% PSA decline (P = .009).

CONCLUSIONS:

In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS and appeared to complement PSA assessment. Cancer 2011. © 2011 American Cancer Society.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Identification of Prognostic Factors

IntroductionThe purpose of this study was to evaluate the effect of prognostic factors on the outcome of patients with MM after ASCT.Patients and MethodsWe analyzed results of 170 consecutive patients (121 male and 49 female) of MM who underwent ASCT. Patients' median age was 52 years (range, 26-68 years). High dose melphalan (200 mg/m²) was used for conditioning. One hundred thirty-two patients (77.6%) had evidence of chemosensitive disease before transplant. Response was assessed using European Group for Blood and Bone Marrow Transplantation criteria.ResultsPost ASCT 44.7% of patients achieved CR, 24.7% had very good partial response (VGPR), and 21.2% had partial response (PR). Presence of pretransplant chemosensitive disease (CR, VGPR, and PR) and transplant within 12 months of diagnosis for years before 2006 were associated with higher response rates on multivariate analysis. At a median follow-up of 84 months, median overall (OS) and event-free survival (EFS) is 85.5 and 41 months, respectively. Estimated OS and EFS at 60 months is 62 ± 0.04% and 41 ± 0.04%, respectively. Patients who responded to transplant (CR, VGPR, and PR) had a longer OS (P < .001) and EFS (P < .001). Additionally, patients who achieved CR post transplant had a longer OS (P < .001) and EFS (P < .001). Patients who received novel agents for induction pretransplant had a longer OS (P < .001) and EFS (P < .002).ConclusionOutcome after ASCT is better for myeloma patients with pretransplant chemosensitive disease and those who achieve CR after transplant.     

Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia

BACKGROUND:

Response and survival in 96 patients with secondary acute myeloid leukemia (sAML) who received aggressive induction chemotherapy was reviewed.

METHODS:

The median follow‐up of survivors was 2.3 years. A total of 70 (73%) patients achieved a morphologic complete remission (CR) confirmed by absence of leukemic blasts by flow cytometry.

RESULTS:

For all 96 patients, the median event‐free survival (EFS) was 8 months, and overall survival (OS) was 13.6 months (range, 1‐119 months). Eight patients died shortly after induction therapy because of disease or side effects, and 13 are currently in continuous first remission. The median disease‐free survival (DFS) for all 70 patients who achieved a morphologic CR was 9 months (range, 1‐51 months), with a 64% chance of surviving 1 year. Patients with AML after previous chemotherapy or radiation therapy had a higher morphologic remission rate compared with those arising from myelodysplastic syndrome or myeloproliferative disease (82% vs 62%; P = .027). However, among the patients from the 2 groups who attained a morphologic remission, there was no difference in terms of CR rate (P = .94), DFS, EFS, or OS (P = .55, .83, and .71, respectively). This is a similar DFS to the group of 7 patients who went directly to ablative allogeneic transplant rather than having induction therapy first. In this population of patients who received aggressive chemotherapy, Charlson comorbidity index or a higher number of factors recognized as high risk in leukemia patients did not affect the chance of OS, DFS, and EFS, although having more recognized leukemia risk factors was related to a lower chance of surviving 1 year. However, it is important to note that those with higher comorbidity indexes were underrepresented in this aggressively treated cohort.

CONCLUSIONS:

The data from the current study demonstrate that many patients with sAML can tolerate aggressive induction therapy and attain remission, but duration of response and the chance of long‐term survival remain poor. Cancer 2009. © 2009 American Cancer Society.     

Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: A retrospective analysis of JALSG‐APL97

For patients with relapsed acute promyelocytic leukemia (APL), all‐trans retinoic acid‐based salvage regimens can achieve second complete remission (CR2), but the optimal post‐remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)‐HSCT, 21 received allogeneic (allo)‐HSCT, and 30 received various regimens other than HSCT. The 5‐year event‐free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non‐HSCT group, 41.7%, 83.3% and 58.3% in the auto‐HSCT group and 71.1%, 76.2% and 9.8% in the allo‐HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo‐HSCT group than in other groups. Allo‐HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation‐related mortality (19%). Among older patients (age ≥40 years), the 5‐year OS was significantly better in the non‐HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.     

Noninvasive imaging with thallium‐201 scintigraphy may not correlate with survival in patients with osteosarcoma

BACKGROUND:

Histologic response to preoperative chemotherapy is a strong prognostic factor for osteosarcoma (OS). Thallium‐201 (Tl‐201) scintigraphic response to initial chemotherapy has previously been described as a predictor of histologic response. In the current study, the authors re‐examined a series of patients studied using Tl‐201 scintigraphy to determine the correlation between changes observed on Tl‐201 scintigraphy and event‐free survival (EFS).

METHODS:

A total of 22 patients with biopsy‐proven OS of the extremity underwent Tl‐201 imaging before and immediately after preoperative chemotherapy. The maximum pixel counts taken over the tumor divided by those taken of a background region yielded a tumor‐to‐background ratio (TBR). The percentage of change in the TBR before and after adjuvant chemotherapy, defined as the alteration ratio (AR), was correlated with EFS.

RESULTS:

The median AR was 85% (range, 28‐100%). The 3‐year EFS was 0.72 (95% confidence interval [95% CI], 0.48‐0.86) and the 5‐year EFS was 0.67 (95% CI, 0.43‐0.86). There was no association between AR and EFS detected in this cohort (hazard ratio, 0.99; 95% CI, 0.95‐1.02 [Somers rank correlation coefficient, 0.15]).

CONCLUSIONS:

Although Tl‐201 scintigraphy was used as a tool for the assessment of response to chemotherapy in patients with OS, the AR did not appear to be predictive of EFS in this small group of patients. It is necessary to use the outcome variables of ultimate interest–EFS and overall survival– and not rely on surrogates for outcome to evaluate potential prognostic factors. Cancer, 2010. © 2010 American Cancer Society.     

抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究

 目的　探讨抗CD20单克隆抗体（利妥昔单抗,商品名：美罗华）联合自体外周血干细胞移植（APBSCT）治疗B细胞非霍奇金淋巴瘤（NHL）的疗效。方法　21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解（CR）,难治性病例为16例,包括11例部分缓解（PR）和5例疾病进展（PD）。在自体造血干细胞动员的第1、8天及预处理的-1、＋7天每天应用利妥昔单抗375 mg／m2。结果　移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存。21例患者中位随访24（1～68）个月,复发、死亡4例（19 %）,其余17例均无病生存,2年无病生存（EFS）和总生存（OS）率均为81.0 %。未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响。结论　APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS。利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建。     

Durable remission with salvage second autotransplants in patients with multiple myeloma

BACKGROUND:

High‐dose chemotherapy with autologous hematopoietic cell transplant (auto‐HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto‐HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined.

METHODS:

The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto‐HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center.

RESULTS:

Median interval between the first and salvage auto‐HCT was 30 months (range, 2‐78 months). Median age at salvage HCT was 54 years (range, 38‐73 years), and median number of salvage treatment regimens was 2 (range, 0‐5). Eleven (25%) patients had high‐risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto‐HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto‐HCT. One patient died within 100 days, for a treatment‐related mortality of 2%. Best responses after salvage chemotherapy + salvage auto‐HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto‐HCT maintenance therapy. Median follow‐up from salvage HCT was 41 months. Kaplan‐Meier estimates of median progression‐free survival (PFS) and overall survival (OS) from time of salvage auto‐HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto‐HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS.

CONCLUSIONS:

In selected myeloma patients, a second auto‐HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens. Cancer 2012;3549–3555. © 2011 American Cancer Society.     

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma

BACKGROUND:

Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R‐EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)‐associated, aggressive B‐cell, non‐Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity.

METHODS:

The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV‐associated NHL who received either R‐CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R‐EPOCH (n = 51; AMC034). Age‐adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/μL vs ≥100/μL), and treatment (R‐CHOP vs R‐EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event‐free survival (EFS) and overall survival (OS).

RESULTS:

Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ≥100/μL. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R‐EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P < .001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P < .01). Treatment‐associated death occurred significantly more often in patients with CD4 counts <50/μL (37% vs 6%; P < .01).

CONCLUSIONS:

The current analysis provided additional level 2 evidence supporting the use of concurrent R‐EPOCH in patients with HIV‐associated lymphoma and a CD4 count >50/μL, and the results support the design of an ongoing phase 3 trial comparing concurrent R‐EPOCH with R‐CHOP in immunocompetent patients with diffuse large B‐cell lymphoma (National Clinical Trial no. NCT00118209). Cancer 2012. © 2011 American Cancer Society.     

Allogeneic hematopoietic stem cell transplantation at the first remission for younger adults with FLT3‐internal tandem duplication AML: The JALSG AML209‐FLT3‐SCT study

In this phase II multicenter study (JALSG AML209‐FLT3‐SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1) for FLT3‐internal tandem duplication (ITD)‐positive AML. Newly diagnosed de novo AML patients with FLT3‐ITD were enrolled at the achievement of CR1 and received allo‐HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17‐49) years, 36 (75%) received allo‐HSCT at a median of 108 days after CR1. The median follow‐up was 1726 days. The primary end‐point, 3‐year disease‐free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%‐57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3‐year overall survival, post‐transplant DFS, and non‐relapse mortality rates were 54.2% (95% CI, 39%‐67%), 58.3% (95% CI, 41%‐72%), and 25.0% (95% CI, 12%‐40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006‐4.099). Neither FLT3‐ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo‐HSCT for FLT3‐ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433.     

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Although preliminary results suggest that allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the low patient number in previous studies had limited ability to evaluate the true benefit of allo HCT in OC. This retrospective multicenter study included 30 patients with OC allografted between 1995 and 2005 to determine the outcome of patients with OC treated with allo HCT. Prior to allo HCT, patients were in complete response (n = 1), partial response (n = 7), stable disease (n = 11) or had progressive disease (n = 13). An objective response (OR) was observed in 50% (95% CI, 33–67) of patients. Three patients of responding patients had an objective response following the development of acute graft‐versus‐host disease (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18–50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year, respectively. With a median follow‐up of 74.5 months (range 16–148), median progression free survival (PFS) was 6 months and median overall survival (OS) was 10.4 months. Patients who developed cGvHD following allo HCT had a significant OS improvement compared to those who did not (17.6 months vs. 6.5 months, p = 0.042). However, PFS was not similarly significantly improved in patients who developed cGvHD (12 months versus 3.7 months, p = 0.81). Allo HCT in OC may lead to graft‐versus‐OC effects. Their clinical relevance remains to be shown.     

Long‐term outcome in localized extranodal mucosa‐associated lymphoid tissue lymphomas treated with radiotherapy

BACKGROUND:

This study was conducted to evaluate the long‐term outcomes in patients with stage IE and IIE mucosa‐associated lymphoid tissue (MALT) lymphomas treated with involved field radiotherapy (RT).

METHODS:

Between 1989 and 2004, 192 patients with stage I and II MALT lymphomas were treated. The report focuses on 167 patients who received RT. The median age of patients was 58 years with a female predominance (2:1). Presenting sites were as follows: orbital adnexa in 71 patients, salivary glands in 28 patients, stomach in 25 patients, thyroid in 21 patients, and other sites in 22 patients. The median dose to nonorbital sites was 30 grays (Gy) (range, 17.5‐35 Gy) and was 25 Gy for the orbit (range, 25‐35 Gy). The median follow‐up was 7.4 years (range, 0.67‐16.20 years).

RESULTS:

Complete response and complete response, unconfirmed (CR/CRu) was noted in 166 (99%) patients. The 10‐year recurrence‐free rate (RFR) was 76%, the disease‐free survival (DFS) rate was 68%, the overall survival (OS) rate was 87%, and the cause‐specific survival rate was 98%. According to presenting site, the 10‐year RFR was 95% for thyroid, 92% for stomach, 68% for salivary glands, and 67% for orbit. Patients with thyroid and gastric MALTs had better outcome compared with patients with MALTs diagnosed at other sites (P = .004). Among those patients who achieved CR, 19% developed disease recurrence (n = 31), chiefly in distant sites or untreated contralateral‐paired organs. At the time of disease recurrence, 7 patients (23%) had transformed to diffuse large B‐cell lymphoma, 2 of whom died of lymphoma. The 5‐year OS rate after treatment failure was 83%.

CONCLUSIONS:

Patients with localized MALT lymphomas are reported to have excellent clinical outcome after moderate‐dose RT, and some are likely cured. In the current study, thyroid and gastric MALTs were found to have significantly less risk of distant recurrence. Despite disease recurrence, the overall survival remains excellent in these patients. Cancer 2010. © 2010 American Cancer Society.     

Romidepsin treatment for relapsed or refractory peripheral and cutaneous T‐cell lymphoma: Real‐life data from a national multicenter observational study

Romidepsin is a class I selective histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for relapsed/refractory (R/R) cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphoma (PTCL), treated with at least one prior systemic therapy. Currently, there is paucity of real‐life data on the efficacy and safety of romidepsin in R/R T‐cell lymphoma. This national, multicenter study presents real‐life data on the efficacy and safety of romidepsin in R/R T‐cell lymphoma. Patients diagnosed and treated with romidepsin for R/R CTCL or PTCL between 2013 and 2018 were retrospectively reviewed. Outcomes included overall survival (OS), event‐free survival (EFS), overall response rate (ORR), complete response (CR), and adverse events. Fifty‐three patients with R/R PTCL (n = 42) or CTCL (n = 11) were included. Among CTCL patients, median OS was not reached, ORR was 25%, and none achieved CR. Among PTCL patients, median OS was 7.1 months, EFS was 1.9 months, ORR rate was 33%, and 12.5% achieved CR. In a univariate analysis, predictors for longer EFS include any response to therapy, number of previous lines, and PTCL subclass (with better results for angioimmunobalstic T‐cell lymphoma). In a univariate and multivariate analysis for OS, treatment response was the only factor predicting OS (OR 4.48; CI 95%, 1.57‐12.79; P = .005). Most grade 3 and 4 adverse events were hematological (35%). Infections were reported in 34% of patients. This real‐life experience with romidepsin confirms the results of the pivotal phase II trials. PTCL subtype and the number of previous lines of therapy have an impact on EFS. In addition, patients who had good response to romidepsin benefited most in terms of both EFS and OS. Efforts should be done to identify those patients.     

Outcome for adolescent and young adult patients with osteosarcoma: A report from the Children's Oncology Group

BACKGROUND:

There are conflicting data regarding age as a prognostic factor in osteosarcoma. The authors conducted a study evaluating the impact of age on prognosis in children and young adults with osteosarcoma enrolled on North American cooperative group trials.

METHODS:

Patients with high‐grade osteosarcoma of any site enrolled on North American cooperative group trials CCG‐7943, POG‐9754, INT‐0133, and AOST0121 were included in this study. Primary tumor site, age, sex, ethnicity, histologic response, and presence of metastatic disease at diagnosis were evaluated for their impact on overall survival (OS) and event‐free survival (EFS).

RESULTS:

A total of 1054 patients were eligible and had complete data available for the study. Age was not significantly associated with any other presenting covariate analyzed except sex. Age 18 or older was associated with a statistically significant poorer EFS (P = .019) and OS (P = .043). The 10‐year EFS and OS in patients <10, 10 to 17, and ≥18 years old were 55%, 55%, 37% and 68%, 60%, 41%, respectively. The poorer EFS in patients ≥18 years old was because of an increased rate of relapse. Presence of metastatic disease at diagnosis, poor histologic response, and pelvic tumor site were also associated with a poorer prognosis. In multivariate analysis, age continued to be associated with poorer EFS (P = .019) and OS (P = .049).

CONCLUSIONS:

In osteosarcoma, age 18 to 30 years is associated with a statistically significant poorer outcome because of an increased rate of relapse. Poorer outcome in adolescent and young adult patients is not explained by tumor location, histologic response, or metastatic disease at presentation. Cancer 2012. © 2012 American Cancer Society.     

Current event‐free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia

BACKGROUND:

Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second‐generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event‐free survival (EFS).

METHODS:

In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front‐line therapy (n = 281) or after failure on interferon‐α (IFN‐α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs.

RESULTS:

For patients who received imatinib after failing on IFN‐α, the 7‐year EFS rate was 61%, whereas the CEFS rate was 69%. The 7‐year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7‐year CEFS rate of 88%.

CONCLUSIONS:

CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI. Cancer 2011. © 2010 American Cancer Society     

Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non‐Hodgkin lymphoma

BACKGROUND:

Marqibo, a sphingosomal/cholesterol encapsulation of vincristine sulfate has targeted, increased, and sustained delivery of vincristine to tumor tissues. A phase 2, open‐label, single‐arm, and multinational study evaluated the efficacy and tolerability of Marqibo as a single agent in patients with multiply relapsed or refractory aggressive non‐Hodgkin lymphoma (NHL).

METHODS:

Eligible patients had relapsed or refractory de novo or transformed aggressive NHL and prior treatment with at least 2 multiagent chemotherapy regimens. Marqibo was administered at 2 mg/m², every 2 weeks, for a maximum of 12 cycles or until toxicity or disease progression.

RESULTS:

One hundred and nineteen patients were enrolled and treated on trial. Ninety‐six had histological confirmed de novo (N = 89) or transformed (N = 7) aggressive NHL. Median number of cycles was 4 (median dose/cycle 4 mg). Overall response (CR and complete response unconfirmed and PR) was 25% (95% confidence interval [CI], 17, 35), CR and complete response unconfirmed confirmed by external reviewers was 5%. Median overall survival was 6.6 months (Kaplan‐Meier estimate, 95% CI, 4.7, 9.8). Grade 3 of 4 neurotoxicity occurred in 32% of patients. All patients had prior neurotoxic agents, and 85% had baseline residual neuropathy symptoms (grades 1‐2) from prior treatment.

CONCLUSIONS:

Marqibo is an active agent in patients with heavily pretreated aggressive NHL, and tolerated at approximately twice the dose intensity of standard vincristine. Its activity supports further investigation as a substitution for vincristine in combination treatment of lymphoid disorders. Cancer 2009. © 2009 American Cancer Society.     

The role of technetium‐99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma

BACKGROUND:

The authors prospectively evaluated the correlation between technetium‐99m methoxyisobutyl isonitrile (^99mTc‐MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC).

METHODS:

Eighty‐six patients with locally advanced NPC underwent single‐photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) ^99mTc‐MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5‐fluorouracil (5‐FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between ^99mTc‐MIBI accumulation in tumors and response to chemotherapy with 5‐FU/DDP was examined.

RESULTS:

Positive accumulation of ^99mTc‐MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5‐FU/DDP chemotherapy in patients who had positive ^99mTc‐MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative ^99mTc‐MIBI accumulation (TUR ≤1.1; 98.7% vs 10%; P < .001).

CONCLUSIONS:

Patients with negative ^99mTc‐MIBI accumulation were resistant to 5‐FU/DDP chemotherapy. ^99mTc‐MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5‐FU/DDP and can help in the selection of patients for induction chemotherapy. Cancer 2011. © 2010 American Cancer Society.     

Two autologous transplants in the treatment of patients with Hodgkin's lymphoma: analysis of prognostic factors and comparison with a single procedure

We summarized registry data of the long term observation of 35 patients treated with two autologous transplants. Prognostic factors for overall survival (OS) and DFS were analyzed. The OS was compared with 105 patients from a single transplant group. Two factors were significant in univariate analysis of DFS after the second transplant: response to the first transplant (complete remission (CR) versus progressive disease (PD) p = 0.041) and the disease status at the time of the second autologous stem cell transplantation (ASCT) (CR versus partial remission (PR) p = 0.004; CR versus PD p = 0.0002). In the multivariate analysis only the last of the parameters remain significant (RR 2.30, p = 0.004, 95% CI; 1.30 - 4.04). In the analysis of OS, two factors were significant in univariate analysis: status of the disease at the first transplant (PR versus PD p = 0.008) and response to the first transplant (CR versus PD p = 0.025). None of those factors remained significant in a multivariate analysis. A probability of 5-year survival after the first transplant in patients treated with two transplants was 83% (95% CI; 70 - 97%). A tendency towards better survival was seen in patients treated with two transplants (p = 0.01). The trend toward better survival from the time of diagnosis is kept for those who entered CR or PR after standard chemotherapy (p = 0.097) but not for the whole group (p = 0.13).     

Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

BACKGROUND:

Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) in patients with nonsmall cell lung cancer (NSCLC).

METHODS:

The authors tested the possibility that nucleotide sequencing may be poorly suited for detection of mutations in tumor samples and found that denaturing high‐performance liquid chromatography (dHPLC) was an efficient and more sensitive method for screening.

RESULTS:

These results suggested that some reports based on standard DNA sequencing techniques may have underestimated mutation rates. In the present report, the authors examined the relationship between the presence and type of EGFR mutations detected by dHPLC and various clinicopathologic features of NSCLC, including response to therapy with EGFR‐TKI. Among 251 patients with advanced disease, 100 individuals received EGFR‐TKI. Those whose tumors harbored a detectable EGFR kinase mutation were much more likely to have a partial response (PR) or stable disease (SD) with EGFR‐TKI therapy than patients whose tumor contained no mutation (80% vs 35%; P = .001). Among the individual genotype subgroups, the frequency of a PR or SD was significantly different between patients with an exon 19 deletion compared with those with no detectable mutation (86% vs 35%; P < .001). Furthermore, patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend toward better EGFR‐TKI response (86% vs 67%; P = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation.

CONCLUSIONS:

Our findings warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types. Cancer 2010. © 2010 American Cancer Society.     

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

Computed tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?

BACKGROUND: The aim of this study was to evaluate the accuracy of computed tomography (CT) and [(18)F]fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) for prediction of progression-free survival of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients after completion of therapy. PATIENTS AND METHODS: CT and FDG-PET were performed in 40 HD, 17 indolent NHL and 44 aggressive NHL patients (29 women, 72 men; aged 41+/-14 years) in a median of 2 months after therapy. Progression-free survival was evaluated using the Kaplan-Meier method. Independent prognostic factors were identified by means of Cox proportional hazards model. RESULTS: CT imaging results were progressive disease (PD) in five, stable disease (SD) in 57, and partial response (PR) or complete remission (CR) in 39 patients. FDG-PET suggested residual lymphoma in 24 patients. Three-year progression-free survival rates after exclusion of five PD patients were: 100% (PET negative; CT: PR or CR), 81% (PET negative; CT: SD), 21% (PET positive; CT: SD) and 0% (PET positive; CT: PR). FDG-PET (P<0.0001) and bulky disease (P <0.05) were identified as independent prognostic variables. CONCLUSIONS: Among lymphoma patients with PR and SD on CT, FDG-PET discriminated those destined to progress into a low risk of < or =20% and a high risk for recurrence of > or =80%.