Concordance in the interpretation of PET after chemotherapy in advanced stage Hodgkin lymphoma

SummaryThe aim was to analyze the degree of agreement between the central review panel and the local PET interpretation within the HD15 trial and its impact on subsequent treatment and progression free survival. Patients, methods: The analysis set consisted of 739 patients with residues ≥ 2.5 cm after 6 or 8 cycles of BEACOPPesc from the HD15 trial performed by the German Hodgkin Study Group. The recommendation for or against further radiotherapy was based on the central [18F]FDG-PET interpretation. Central PET interpretation was compared to the local PET interpretation and concordance was measured using Cohen's Kappa coefficient. Prognostic impact of the analysis of concordance between local and central PET interpretations was evaluated using progression free survival (PFS); groups were compared with the log rank test. Results: The central panel rated 548 of 739 patients (74%) as PET negative. Of these, 513 were also rated as PET negative in the local PET interpretation. PET positivity was seen by central reviewers in the remaining 191 patients (26%), in concordance with local reviewers in 155 cases. Even though substantial agreement was found (Cohen's Kappa 0.81), the interpretation of the central PET review panel led to a different therapeutic recommendation in 71/739 (10%) patients. PFS was equally high in groups in which the therapeutic regime had been changed on the basis of the central panel decision. Conclusion: High concordance is found between local and central reviewers with regard to PET interpretation in residual tissue after intense chemotherapy. The existence of the central PET review panel allows the identification of additional patients as PET negative so that radiotherapy can be safely omitted (35 of 548 patients = 4.7%).

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Analysis of Kohne's prognostic index in KRAS wild-type patients with metastatic colorectal cancer (mCRC) treated with salvage-line cetuximab-based regimen: HGCSG0901.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.634 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 634-634

Author(s):

Ayako Doi ◽

Satoshi Yuki ◽

Yasushi Tsuji ◽

Takahide Sasaki ◽

Hiraku Fukushima ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Index ◽

Progression Free Survival ◽

Cox Proportional Hazards Model ◽

Rank Test ◽

Prognostic Impact ◽

Wild Type ◽

Free Survival ◽

Significant Difference

634 Background: In the treatment for mCRC, it is essential for understanding the prognosis of each individual patient. Köhne’s index (KI) based on performance status, white blood cell count, alkaline phosphatase and number of metastatic sites has been previously proposed. However, in the salvage setting, the validity of KI has not been reported in patients treated by cetuximab-based chemotherapy. Methods: 269 patients with mCRC treated by cetuximab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS wild-type patients who were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. The analysis was also designed to determine whether the Köhne’s classification could be extended to other endpoints such as progression-free survival. Results: All data were available for prognostic categorization in 127 patients. Median overall and progression-free survival was 9.8 and 4.2 months. The distribution and median survival / progression-free survival for KI were as follows: low risk (L) (n = 40; 13.1/5.1 months), intermediate risk (I) (n = 17; 9.6/3.5 months), and high risk (H) (n = 70; 7.6/4.1 months). For overall survival, there was significant difference between L and H (p = 0.004), but not between L and I (p = 0.213), and between I and H (p = 0.321). For progression-free survival, there was tended to difference between L and H (p = 0.083), but not between L and I (p = 0.392), and between I and H (p = 0.630). In Cox multivariate analysis, KI showed an independent prognostic impact (HR 1.370, p = 0.010), but not predictive impact (HR 1.147, p = 0.212). Conclusions: In this analysis, KI might be a prognostic factor in salvage treatment with cetuximab-based regimen, but no effect predicted impact. Moreover, the prospective evaluation is needed for the further validation.

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LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000029 ◽

2021 ◽

pp. 1-9

Author(s):

Ankita Gupta ◽

Budhi Singh Yadav ◽

Nagarjun Ballari ◽

Namrata Das ◽

Ngangom Robert

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Progression Free Survival ◽

Rank Test ◽

Karnofsky Performance Score ◽

Breast Cancer Patients ◽

Free Survival ◽

Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

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Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.51 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 51-51

Author(s):

Richard Gagnon ◽

Nimira S. Alimohamed ◽

Alexander Watson ◽

Eugene Batuyong ◽

Alyssa Chow ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Outcomes ◽

Real World ◽

Retrospective Cohort ◽

Cohort Analysis ◽

Progression Free Survival ◽

Rank Test ◽

Castration Resistant Prostate Cancer ◽

Survival Times ◽

Free Survival

51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p < 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.

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Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies

Melanoma Research ◽

10.1097/cmr.0000000000000739 ◽

2021 ◽

Vol 31 (3) ◽

pp. 208-217

Author(s):

Alexandra Frelau ◽

Eva Jali ◽

Boris Campillo-Gimenez ◽

Marc Pracht ◽

Marc Porneuf ◽

...

Keyword(s):

Metastatic Melanoma ◽

Progression Free Survival ◽

Prognostic Impact ◽

Free Survival ◽

Thyroid Dysfunctions

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G-8 Geriatric Screening Tool Independently Predicts Progression-Free Survival in Older Ovarian Cancer Patients Irrespective of Maximal Surgical Effort: Results of a Retrospective Cohort Study

Gerontology ◽

10.1159/000520328 ◽

2021 ◽

pp. 1-10

Author(s):

Katharina Anic ◽

Sophie Birkert ◽

Mona Wanda Schmidt ◽

Valerie Catherine Linz ◽

Anne-Sophie Heimes ◽

...

Keyword(s):

Ovarian Cancer ◽

Global Health ◽

Screening Tool ◽

Prognostic Index ◽

Progression Free Survival ◽

Assessment Tools ◽

Prognostic Impact ◽

Free Survival ◽

Geriatric Screening ◽

The Impact

Background: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). Methods: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Results: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056–3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. Conclusions: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

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Overexpression of the OCT-1 Gene Is a Biomarker Associated with Poor Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) - Data from a Retrospective Cohort from Latin America: Defining a Very High-Risk Clinical-Molecular Subgroup

Blood ◽

10.1182/blood-2020-142715 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 41-42

Author(s):

Luis Alberto de Padua Covas Lage ◽

Gisele Rodrigues Gouveia ◽

Suzete Cleusa Ferreira ◽

Sheila Aparecida Coelho de Siqueira ◽

Abrahão Elias Hallack Neto ◽

...

Keyword(s):

Gene Expression ◽

High Risk ◽

B Cell ◽

Univariate Analysis ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Prognostic Impact ◽

Molecular Subgroup ◽

Free Survival ◽

Very High

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.

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AGO2 expression levels and related genetic polymorphisms: influence in renal cell progression and aggressive phenotypes

Pharmacogenomics ◽

10.2217/pgs-2021-0072 ◽

2021 ◽

Author(s):

Ana Luísa Teixeira ◽

Ana Sofia Patrão ◽

Francisca Dias ◽

Carlos Silva ◽

Isabel Vieira ◽

...

Keyword(s):

Cancer Progression ◽

Renal Cell ◽

Progression Free Survival ◽

Rank Test ◽

Mrna Levels ◽

Free Survival ◽

Increased Risk ◽

Cell Progression ◽

Progression Risk ◽

Circulating Levels

Aim: Renal cell carcinoma (RCC) is the most lethal urological cancer and up to 40% of patients submitted to surgery will relapse. Thus, the study aim was to analyze the associations of AGO2 SNPs with RCC patients’ prognosis, and evaluate their effect on AGO2 mRNA levels. Materials & methods: The AGO2 rs4961280, rs3928672 and rs11996715 polymorphisms and the relative quantification of AGO2 mRNA levels were analyzed by real-time PCR. Results: We observed that AGO2 rs4961280 AC + AA genotypes carriers presented a higher cancer progression risk (OR= 3.13, p < 0.001), a reduced progression-free survival (log rank test, p = 0.003) and an increased risk of an early relapse (HR= 2.26, p = 0.008). In fact, these patients also presented higher circulating levels of AGO2 mRNA (p = 0.043), with the high levels being associated with more aggressive tumors. Conclusion: The AGO2 rs4961280 AA/AC genotypes are unfavorable RCC prognostic biomarkers, with the AGO2 levels being a useful RCC aggressive phenotype biomarker.

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Dynamic Changes in Prostate-Specific Antigen After Androgen Deprivation Therapy for Prostate Cancer are Strongly Associated with Biochemical Progression-Free Survival: A Multicenter Retrospective Analysis

10.21203/rs.3.rs-820937/v1 ◽

2021 ◽

Author(s):

Mingqiu Hu ◽

Yifeng Mao ◽

Kaizhong Zhang ◽

Chao Guan ◽

Aiming Wu

Keyword(s):

Prostate Cancer ◽

Survival Curve ◽

Specific Antigen ◽

Progression Free Survival ◽

Androgen Deprivation ◽

Prognostic Indicators ◽

Rank Test ◽

Dynamic Changes ◽

Free Survival ◽

Biochemical Progression

Abstract Objectives: The risk factors for prostate cancer to progress to castration-resistant prostate cancer after androgen deprivation treatment (ADT) are still not to be well defined. We conducted this investigation in an attempt to determine factors that predicted the prognosis in a series of patients with prostate cancer after ADT. Methods: We retrospectively analyzed the database of patients treated with androgen deprivation prostate cancer who were hospitalized in the Second Affiliated Hospital of Bengbu Medical College and Maoming People's Hospital from 2015.1.1 to 2020.12.30. PSA dynamic changes, including nadir PSA (nPSA), time to nadir PSA (TTN), were examined regularly. Cox risk proportional regression model was used for univariate and multivariate analysis; Kaplan-Meier survival curve and Log-rank test were used to compare and analyze differences in biochemical progression-free survival (bPFS) between groups. Results: During the follow-up with a median time of 43.5 months, a total of 163 men were included in the study. The median bPFS of the two groups with nPSA lower than 0.2ng/ml and ≥0.2ng/ml were 27.6 months and 13.5, respectively, with significant differences between the groups (Log-rank p<0.001); The median bPFS of the two groups with TTN ≥9 months and less than 9 were 27.8 months and 13.5 months, respectively, with significant differences between the groups (Log rank p<0.001). Conclusions: PSA dynamic changes after androgen deprivation treatment of prostate cancer can be used as prognostic indicators for bPFS. The lower the nadir PSA value and the longer the time to nadir, the longer the bPFS of patients with prostatic cancer after androgen deprivation treatment.

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BIOM-38. THE PROGNOSTIC ROLE OF THE IMMUNOHISTOCHEMICAL MARKERS H3K27me3, SSTR1-5 AND BAP1 IN MENINGIOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.069 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi19-vi19

Author(s):

Felix Behling ◽

Christina Fodi ◽

Mirjam Renovanz ◽

Frank Paulsen ◽

Marco Skardelly ◽

...

Keyword(s):

Tumor Recurrence ◽

Prognostic Markers ◽

Somatostatin Receptors ◽

Progression Free Survival ◽

Prognostic Impact ◽

Potential Candidate ◽

Primary Tumors ◽

Free Survival ◽

Immunohistochemical Markers ◽

Increased Risk

Abstract Meningiomas are the most common primary tumors of the nervous system. These slow growing tumors arise from the meninges. Most patients can be cured by surgical excision. Yet, approximately 20% of patients suffer tumor recurrence. Prognostic markers are warranted to facilitate the identification of patients with an increased risk of tumor recurrence. Immunohistochemical markers are very interesting candidates in this regard and could be integrated into the routine clinical workflow as an inexpensive tool for prognostication and risk stratification. We analyzed the prognostic impact of the immunohistochemical expression of H3K27me3, somatostatin receptors 1-5 and BAP1 in the Tübingen meningioma cohort including > 1200 meningiomas. We identified an independent negative prognostic impact of the loss of H3K27me3. An increased expression score for SSTR2A was associated with a shorter progression-free survival. Higher expression of SSTR5 indicated a more favorable prognosis. The loss of BAP1 expression in meningioma cells was a negative prognostic factor with a shorter progression-free survival. Taken together, we present potential candidate prognostic markers that could be further investigated in prospective cohorts to determine their clinical utility.

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Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.5.1089 ◽

1995 ◽

Vol 13 (5) ◽

pp. 1089-1095 ◽

Cited By ~ 8

Author(s):

W P Vaughan ◽

E Kris ◽

J Vose ◽

P J Bierman ◽

P Gwilt ◽

...

Keyword(s):

Phase I ◽

Continuous Infusion ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

Rank Test ◽

High Dose ◽

Hematopoietic Stem ◽

Free Survival ◽

Stem Cell Rescue

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.

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