Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma

BACKGROUND: Despite improved detection of mantle cell lymphoma (MCL), results of its treatment with conventional therapies remain disappointing and the survival rate poor. The role of high-dose chemotherapy has recently been investigated but no potential benefit has been clearly established. We report here our experience with MCL patients treated with intensive chemotherapy and autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Of the 16 MCL patients who received high-dose chemotherapy and ASCT beginning in 1989, six were treated in first-line and 10 in sensitive relapse. Twelve of 16 patients received regimens which included total body irradiation. All patients received peripheral blood stem cells (PBSC) with the exception of one, who underwent bone marrow transplantation. RESULTS: Three patients died of toxic effects of treatment, Three months after transplant, seven achieved complete response, (CR) and two partial responses (PR), two were stable and two had progressed. With a median follow-up after transplant of 22 months, five of the six surviving patients were without progression, and three were in CR. The median times for event-free survival (EFS) and overall survival (OS) were, respectively, 249 and 317 days. The expected three-year EFS and OS were 24%. The median survival after diagnosis was only 29 months. None of the criteria appeared to be significantly associated with a better outcome, but first-line intensification and a short delay after initial diagnosis may be favorable. CONCLUSION: In this study we were not able to confirm the hypothetical benefit of high-dose chemotherapy and PBSC transplantation in mantle cell lymphoma, even though this approach may be promising in a subgroup of patient.     

Burkitt's lymphoma in adults with and without human immunodeficiency virus infection: a single-institution clinicopathologic study of 75 patients

BACKGROUND: Burkitt's lymphoma (BL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma (NHL) in the general population and for 35-40% in the setting of human immunodeficiency virus (HIV) infection. The authors report a 9-year single-institution experience with 75 adult BL patients (46 with and 29 without HIV infection) and compare the clinical and pathologic features of the disease in the two groups of patients. METHODS: Between May 1987 and June 1995, 131 patients with HIV infection and systemic NHL were diagnosed and treated at the National Cancer Institute in Aviano, Italy. In 46 cases (35%), the diagnosis was BL. During the same period, 29 of 1004 HIV negative NHL patients (2.8%) were diagnosed with BL and treated at the same institution. RESULTS: No statistical differences were found in the general characteristics of the two groups at the time that BL was diagnosed. Complete response rate was significantly lower for patients with HIV infection than for those without HIV infection (40% vs. 65%, P = 0.03). The median overall survival was significantly shorter for patients with HIV infection (7 months vs. not yet reached, P = 0.0001). However, the disease free survival (DFS) at 4 years was identical for the two groups of patients (74% for HIV positive patients vs. 73% for HIV negative patients, P = 0.70). CONCLUSIONS: The data from this study show that patients with BL with and without HIV infection share similar clinicopathologic characteristics at presentation. Although the median overall survival is significantly shorter for patients with HIV infection, the DFS is identical for both groups.     

Reassessment of non-hodgkins's lymphoma with a "nodular" growth variant: a clinicopathologic study of follicular, mantle cell and marginal zone lymphomas prospectively diagnosed with multiparameter analyses

Although three subtypes of non-Hodgkin's lymphoma (NHL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), are now well recognized as independent categories, their biological behavior has not been fully compared. One of the reasons for this may be that subclassification by histological examination alone is often difficult since they all have a common variant of a "nodular" growth pattern and occasionally show similar cytological morphology. Recently, we reviewed patients with FL, MCL and MZL, who were prospectively diagnosed, using multiparameter analyses with unfixed fresh biopsy materials. Of 407 NHL patients, 101 (24.8%) belonged to these three categories and 80 could be followed; FL (n=27), MCL (n=27) and MZL (n=26). Twenty eight cases with diffuse large B-cell (DL-B) lineage lymphoma were selected as control at random. The frequency of the MCL patients with performance status (PS) 2 to 4 (41%) was significantly higher than MZL patients (4%) [P< 0.001]. The 3 year survival rate with FL, MCL, MZL and DL-B was 71.5%, 57.4%, 93.3% and 53.1%, respectively. The survival rate for MZL was significantly better than both FL (p = 0.048) and MCL (p = 0.0085). Significant differences were also found in the overall survival rates among the four risk groups as defined by the International Index [I2](low, low-intermediate, high-intermediate and high; 97.4%, 79.6%, 39.4% and 18.2%, respectively). A multivariate analysis revealed that the International Index may be a significant predictor for short survival (p=0.0001) in the patients with FL, MCL or MZL. These results suggest that MZL shows an apparently better prognosis than FL and MCL and is found to be a prognostically independent category. In contrast, the clinical outcome in MCL is the worst among the three subtypes and was closer to that of DL-B. The International Index can be applied to a wide spectrum of NHL, including MCL, MZL and FL, to and can predict prognosis in these cases.     

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.     

Long term follow-up and late complications of 2-chlorodeoxyadenosine in previously treated, advanced, indolent non-Hodgkin's lymphoma

BACKGROUND: The aim of this study was to determine the long term outcome and toxicities after the administration of 2-chlorodeoxyadenosine (2-CdA) to patients with previously treated, advanced, indolent non-Hodgkin's lymphoma (NHL). METHODS: Twenty-two patients (median age, 55 years) with relapsed or refractory low grade NHL (median disease duration, 2.8 years) were treated with 2-CdA by continuous infusion at 0.1 mg/kg/day over 5 or 7 days every 28 days, for a maximum of 6 cycles. RESULTS: The overall response rate was 45%. Two patients (9%) achieved a complete response (CR), 8 patients (36%) achieved a partial response, and 12 patients (55%) had no response. The two patients achieving CR have remained in CR for 46 and 38 months, respectively. Freedom from treatment failure at 24 months was 32%. Overall survival at 24 months was 59%. Three patients developed second malignancies: acute myelogenous leukemia (AML), myelodysplastic syndrome, and a cutaneous lymphoproliferative disorder. Fourteen patients have died after a median follow-up of 28 months (range, 3.9-49.2 months) due to progressive NHL (11 patients), infection (2 patients), and AML (1 patient). CONCLUSIONS: 2-CdA is an active agent for patients with previously treated, advanced, indolent NHL and may result in lasting remissions. Late complications following treatment may include delayed bacterial, fungal, or viral infection. Determination of whether the second malignancies that occurred in three patients reported herein were related to treatment with 2-CdA will require further study.     

A DR17-restricted T cell epitope from a secreted Mycobacterium tuberculosis antigen only binds to DR17 molecules at neutral pH

Mantle cell lymphoma (MCL) was first described as a distinct biological entity on the basis of its association with the t(11;14)(q13;q32) resulting in over-expression of the cyclin D1 gene. Recognition of the morphological, immunophenotypic and clinical characteristics of MCL has enabled the accurate diagnosis of this entity and appreciation of its poor prognosis. Most published series of patients with MCL have used anthracycline-containing regimens. In contrast the British National Lymphoma Investigation (BNLI) group have treated 65 patients with MCL with non-intensive 'low-grade lymphoma' therapy. The median overall survival of 57 months and progression-free survival of 24 months compares favourably with the more intensively treated series. Although the disease was generally more aggressive than other low-grade lymphomas, some patients were asymptomatic and had indolent disease. When compared to 1853 patients with non-MCL low-grade lymphomas entered on the BNLI database, patients were found on average to be older (P=0.02), to have more extranodal disease (P<0.00001), and a higher proportion to have a raised ESR (P=0.02) and a low serum albumin (P=0.002). Multivariate analysis of significant prognostic markers in all BNLI low-grade lymphomas failed to identify MCL as an independent prognostic factor.     

Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group

PURPOSE: To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas (FCLs) for their features of clinical presentation, response to chemotherapy, and prognosis on the basis of a prospective randomized clinical trial. PATIENTS AND METHODS: Patients with MCL and FCL who entered onto the prospective randomized comparison of cyclophosphamide, vincristine, and prednisone (COP) versus prednimustine and mitoxantrone (PmM) followed by a second randomization for interferon (IFN) maintenance versus observation only. RESULTS: One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL. With FCL, both sexes were equally affected (men, 47%); patients with MCL were predominantly men (78%; P < .0004) and had a higher median age (64 v 53 years; P < .0001). Patients with MCL also had more widespread disease, reflected by the proportion of patients with two or greater extranodal manifestations (43% v 21%; P < .005) and nine or greater involved nodal areas (64% v 45%; nonsignificant [NS]). Response to chemotherapy was significantly lower in patients with MCL (complete remission [CR] + partial remission [PR], 69% v 88%; P < .05) and occurred at a slower pace. Patients with MCL also had a shorter event-free interval (median, 8 v 24 months; P < .0001) and overall survival (median, 28 v 77 months; P < .0001). In both subtypes, however, patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60% for MCL and greater than 75% for FCL. CONCLUSION: MCL and FCL differ substantially in their features of presentation, response to chemotherapy, and long-term prognosis. The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies.     

Negative regulation of Apo A-I gene expression by retinoic acid in rat hepatocytes maintained in a coculture system

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently recognised as a distinct disease entity. Little is known about the prognostic factors and optimal treatment of MCL. The aim of this study was to analyse retrospectively the clinical features and effect of treatment in 94 MCL patients diagnosed and treated in one centre between 1980 and 1996, and to find out different factors influencing the treatment results and prognosis. The median age of the patients was 66 years, and 77% were over 60 years old. Of the patients, 76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B symptoms were present in 35% of the cases. Bone marrow infiltration was found in 61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved complete remission with first- or second-line therapy. The median duration of remission, time to treatment failure (TTF), and survival were 28, 18, and 41 months, respectively. In multivariate analyses, age, stage and leukaemic disease were significantly associated with TTF, and age, stage, leukaemic disease and lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL. None of the conventional chemotherapies seems curative. A prospective randomised trial should be made to evaluate the benefit of anthracycline-containing regimens in MCL.     

非霍奇金淋巴瘤中枢神经系统累及的诊断和预防

非霍奇金淋巴瘤(NHL)患者中枢神经系统(CNS)累及预后不良,其中位生存期2～6个月.与NHLCNS累及相关参数是年轻、进展期、累及结外部位数、乳酸脱氢酶(LDH)增高和国际预后指标(IPI)积分.最有希望的治疗为自体造血于细胞移植,可延长中数生存期10～26个月.处于CNS侵袭高危状态的某些NHL亚型患者需要早期进行CNS预防,如伯基特淋巴瘤(BL)和淋巴母细胞淋巴瘤(LBL).弥漫性大B细胞淋巴瘤(DLBCL)初期治疗时是否需应用CNS预防久有争议,因为它属于CNS累及(≈5%)的低危群体.危险模式的确定有助于预示NHL的CNS复发.     

硼替佐米治疗套细胞淋巴瘤的分子学机制

套细胞淋巴瘤(MCL)是生存期最短的非霍奇金淋巴瘤(NHL),目前尚不能根治.硼替佐米是第一个用于治疗血液系统恶性肿瘤的蛋白酶体抑制剂,主要用于多发性骨髓瘤(MM)及复发难治性MCL的治疗.探讨硼替佐米治疗MCL的相关机制,其中包括调节细胞周期、影响细胞凋亡、干扰MCL的微环境以及与其他抗肿瘤药物的协同作用等,有助于未来合理应用硼替佐米治疗MCL.     

A radioreceptor assay for mass measurement of inositol (1,4,5)-trisphosphate using saponin-permeabilized outdated human platelets

PURPOSE: To evaluate the therapeutic efficacy of moderate-dose total abdominopelvic irradiation (TAI) in a retrospective series of pretreated non-Hodgkin's lymphomas (NHL). METHODS AND MATERIALS: From 1977 to 1994, 45 patients received TAI after failure of chemotherapy (CT). According to the Working Formulation, 10 patients were diagnosed with class A (group I), 19 with class B, C, or D (follicular) (group II), and 16 with class E or more severe (group III) NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total dose of 20 Gy. RESULTS: Mean follow-up after TAI was 102 months (range 8-156). For the entire group, the complete response (CR) rate was 66%, the partial response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free survival (DFS) 29%, and median survival 32 months. When results between subgroups were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and survival was statistically higher in group II than in groups I and III: 10-year OS 52% vs. 10% (p < 0.01) and 31% (p < 0.05), respectively, 10-year DFS 37% vs. 10% (p < 0.03) and 19% (p < 0.05), respectively. Grade III or IV complications were gastrointestinal in 27% of patients and hematologic in 25%. CONCLUSION: Large-field irradiation in moderate doses could provide an alternative to bone marrow transplantation in refractory NHL, especially in cases showing a follicular growth pattern.     

Adrenal insufficiency as a manifestation of disseminated non-Hodgkin's lymphoma

OBJECTIVE: To analyze the clinical characteristics, laboratory features, and outcome in five patients who had biochemically proven adrenal insufficiency attributable to pathologically confirmed non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: We retrospectively reviewed the medical records of all patients at Mayo Clinic Rochester during the period from 1976 to 1994 to identify those with both NHL, as listed in the surgical pathology tissue registry, and adrenal insufficiency. Histologically, the patients were classified on the basis of the working formulation and the revised European-American lymphoma classification. RESULTS: Three patients had diffuse large cell NHL, one patient had small noncleaved NHL, and one patient had cutaneous T-cell NHL. All five patients had stage IV disease. Adrenal insufficiency was confirmed by morning and evening determinations of serum cortisol levels and cosyntropin stimulation tests. All patients demonstrated loss of circadian rhythm. The median age of the patients was 77 years (range, 60 to 89). Three of the five patients died without treatment from 5 to 22 days after assessment. One patient died of a cerebrovascular accident. Despite initiation of chemotherapy, two patients died of progressive NHL at 7 weeks and 7 months. CONCLUSION: In our experience, biochemically proven adrenal insufficiency in patients with NHL is a manifestation of clinically advanced disease in elderly patients. A stepwise diagnostic approach is critical for the appropriate management of such patients.     

Molecular and cellular mechanism of angiotensin II-mediated apoptosis

We hypothesized that the conventional ProMACE-CytaBOM regimen could be improved by administering all drugs on d1 with the S-phase agents first in the sequence, prednisone d2-6 only, increasing doxorubicin to 50 mg/m2, and adding G-CSF d2-13 to ameliorate neutropenia. This regimen was tested in a Phase I study of 20 patients (pt) with non-Hodgkin's lymphoma (NHL). The median age was 61 yrs (range, 29-79). Four pt had low grade and 16 intermediate/high NHL. The International Prognostic Index was low in 6 cases, low-intermediate in 12, and high-intermediate in 2. Twelve pt received > or =6 cycles; 4 had 5 cycles, 3 had 4 cycles, and 1 received only 1 cycle. Sixteen pt received subsequent cycles without delay. The response rate was 95% (19/20) with 12 CR and 7 PR; one pt progressed during treatment. After a median follow-up of 30 months, 85% (17/20) remain alive. This higher dose ProMACECytaBOM regimen can be given to older adult patients in an outpatient setting. Phase III studies would be required to determine if it produces a superior overall survival compared to other regimens.     

Characterization of anticapsular monoclonal antibodies that regulate activation of the complement system by the Cryptococcus neoformans capsule

PURPOSE: To evaluate the effectiveness of adding interferon (IFN) alfa-2b to chemotherapy in the induction treatment of low-grade non-Hodgkin's lymphoma (NHL), and to assess the role of maintenance IFN. PATIENTS AND METHODS: A multicenter, two-phase controlled trial with double randomization was conducted in 155 patients with low-grade NHL. In the first randomization, 78 patients received cyclophosphamide, vincristine, and prednisone (CVP) and IFN, 3 MU/m2 three times a week for 3 months, and 77 patients received CVP alone. Responding patients were randomized to receive IFN for 1 year versus observation. RESULTS: Of 144 assessable patients, 73 received CVP + IFN and 71 received CVP. Responses were similar: CVP + IFN 79% versus CVP 76% (P = .62). The number of patients who did not complete the treatment was higher in the CVP + IFN group than in the CVP group (18% v 4%; P = .009), although the received dose-intensity of chemotherapy was comparable. Duration of response and progression-free survival (PFS) were significantly higher in the CVP + IFN group than in the CVP group (P = .0004). However, we observed no differences in overall survival (OS) (P = .30), with a median follow-up for the surviving patients of 3 years. Grade 3/4 granulocytopenia was the most frequent toxicity and was similar in both groups (33% v32%). Eighty-three (74%) of the 112 responding patients were randomized to maintenance IFN or observation. The duration of response was similar between 42 patients that received IFN compared with 41 control patients (P = .83), independently of treatment previously administered. CONCLUSION: Adding IFN alfa-2b to induction CVP in low-grade NHL did not induce a higher response rate, but it significantly increased the duration of the responses. We found significant differences in PFS that favored the patients who received CVP + IFN, but not in OS. To date, no additional benefit has been seen from the administration of IFN for maintenance.     

Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants

PURPOSE: Clinical data and histologic material were retrospectively analyzed in 46 cases of previously untreated mantle cell lymphoma (MCL) to more fully characterize the clinical response pattern of these lymphomas and to determine whether growth pattern significantly affected clinical outcome. MATERIALS AND METHODS: The histologic pattern was classified as diffuse (61%), nodular (13%), and mantle zone (26%) in accordance with stated criteria. RESULTS: Bone marrow infiltration was detected in 69% of cases; the frequency of involvement correlated with histologic pattern, being most common in diffuse variants and least common in mantle zone variants. Other sites of extranodal involvement were observed in 50% of cases. Cyclin-D1 staining revealed nuclear positivity in 23 of 25 patients (92%) and no difference was observed between the various histologic patterns. Rearrangement at the bcl-1 major translocation cluster (MTC) was detected in seven of 21 cases, without regard for histologic pattern. Complete response rates to doxorubicin-based regimens showed a striking correlation with histologic pattern. Seventy-three percent of patients with a mantle zone pattern attained a complete response compared with only 25% of patients with a nodular pattern and 19% with a diffuse pattern. Three-year survival rates were 100%, 50%, and 55% for patients with mantle zone, nodular, and diffuse histologic patterns, respectively. CONCLUSION: We conclude that (1) diffuse and nodular MCL are associated with a poor treatment response and a poor overall survival rate; (2) the mantle zone variant exhibits the clinical attributes of a low-grade lymphoma; and (3) the poor survival rates of patients with nodular and diffuse MCL suggest that these variants be classified as intermediate-grade lymphomas. However, the trend of the time to treatment failure curve does not indicate that current regimens can cure MCL.     

MACOP-B and involved field radiation therapy is an effective therapy for primary mediastinal large B-cell lymphoma with sclerosis

PURPOSE: To evaluate the clinical features of presentation and the response to two different third-generation regimens (F-MACHOP and MACOP-B) of primary mediastinal large B-cell lymphoma (MLBCL), a recently defined distinct clinicopathological entity of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-seven consecutive patients with MLBCL, eight male and 29 female (F/M ratio 1:3.5) with a median age of 35 years, were enrolled in the present study. Thirty-five (94.5%) patients presented disease confined to thorax, with chest symptoms of a rapidly enlarging mass in the mediastinum in 70% and superior vena cava syndrome (SCVS) in 43% of these patients. The first 10 patients received F-MACHOP and the succeeding 27 patients MACOP-B chemotherapy, associated in 24 (88.8%) with involved field radiation therapy (IFRT). 67Gallium scan was routinely performed pre- and post-IFRT in 18 patients. RESULTS: All 37 patients were assessable for response: 10 of 10 (100%) in the F-MACHOP and 26 of 27 (96.3%) in the MACOP-B group achieved overall responses (CR + PR). Three of 24 (12.5%) patients in PR after chemotherapy obtained CR after IFRT. Persistent Gallium avidity was observed in 16 patients after chemotherapy and in only four patients after IFRT. Thus far, four of the 10 F-MACHOP and two of the 26 MACOP-B responders have presented disease progression. The probability of progression-free survival (PFS) was 91% and 60% (P < 0.02) while overall survival (OS) was 93% and 70% (P = n.s.) at a mean follow-up of 27 and 52 months in the MACOP-B + IFRT and F-MACHOP groups, respectively. CONCLUSION: MACOP-B + IFRT has proved to be a highly effective and less toxic therapeutic approach for primary MLBCL and appears to be superior to other third-generation chemotherapy regimens.     

Suppression of cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia

PURPOSE: To investigate whether cytogenetic clonal evolution can be suppressed with interferon alfa (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Ninety patients with CML and cytogenetic clonal evolution who received IFN-alpha-based regimens were analyzed. Clonal evolution was defined as the presence of karyotypic abnormalities in addition to the Philadelphia (Ph) chromosome. Patients were evaluated for the suppression of cytogenetic clonal evolution after therapy, the cytogenetic response, and survival. RESULTS: The median age of the population was 39 years (range, 15 to 70 years), median time from diagnosis to clonal evolution 14 months (range, 0 to 145 months), and median percentage of abnormal metaphases 18% (range, 4% to 100%). Fifty six patients (62%) achieved some suppression of cytogenetic clonal evolution; in 41 patients (46%), the suppression was complete. The overall median survival was 51 months, with 43% alive at 5 years. Patients who achieved a complete suppression of cytogenetic clonal evolution had a median survival of 66 months, with 51% alive at 5 years. Characteristics associated with a better response include a lower percentage of abnormal metaphases, time to cytogenetic clonal evolution of 24 months or less, and absence of other features of accelerated disease. A prognostic classification for cytogenetic clonal evolution defined three groups with complete response (CR) rates of 85%, 34%, and 0% (P < .0001) and median survival times of 58, 31, and 30 months, respectively (P=.02). CONCLUSION: Patients with cytogenetic clonal evolution can respond to IFN-alpha therapy, and this response is associated with longer survival. A previously described prognostic model separates patients into subsets with different probabilities of response to IFN-alpha and survival.     

Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia

The toxicity and therapeutic activity, including the effect on quality of life, of the carboplatin-oral etoposide combination, given with an intrapatient dose escalation, was tested in 38 non-small cell lung cancer (NSCLC) patients aged over 70 years, and in 8 younger patients with a performance status of 2. In the absence of grade 3-4 toxicity, doses were escalated as follows: first course (carboplatin AUC 4; etoposide 50 mg twice daily orally days 1-14); second course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-14); third course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-21). A total of 141 chemotherapy cycles were delivered. The treatment was, in general, well tolerated and no toxic deaths occurred. More than 60% of patients received 100% of the planned dose intensity. Transient grade 4 neutropenia or thrombocytopenia occurred in 6 and 2 patients, respectively, but only 2 patients had to be hospitalised because of fever. All patients were evaluated for activity on an 'intention to treat basis'. Ten partial responses and 20 stable disease were recorded, for an overall response rate of 22% (95% confidence interval (CI) = 11-36). 9/38 (24%; 95% CI = 12-41) elderly patients obtained a partial response. The median response duration was 4 months. A quality of life improvement was observed in 19 of the 46 enrolled patients (41%; 95% CI = 27-57), and 15/46 (33%; 95% CI = 19-48) showed a performance status improvement. The quality of life score improved in 17/38 (45%) elderly patients. 8/10 responders and 11/20 patients with stable disease showed a concomitant improvement in quality of life. At a median potential follow-up of 16 months (range 2-21), 31 patients had had progression of disease and 23 had died, for a median time to progression (TTP) and overall survival (OS) of 5 and 10 months, respectively. The median survival time was 11 months in the elderly patients. The median time to subjective impairment (TSI) was 6 months (7 months in the elderly group). One-year estimated TTP, TSI and OS rates were 22, 29 and 41%, respectively. At multivariate Cox analysis, a > 25% improvement in the quality of life score was more predictive of a better survival outcome than the response achievement.