Months For Partial Responders Research Articles

Outcomes of Adult Burkitt Lymphoma Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT) in CR1 Versus ≥ CR2 - a Single Institution Retrospective Analysis

Introduction Burkitt lymphoma (BL) is a rare, aggressive B-cell lymphoma with protean clinical presentation accounting for Methods After regulatory approval, clinical and outcome data for BL patients who underwent HCT from 2000-2019 were collected. Survival outcomes were compared between patients who achieved complete response (CR1), ≥ CR2 and partial response (PR) prior to HCT. Patients who achieved CR after induction chemotherapy were considered CR1; patients requiring more than 1 line of chemotherapy to achieve CR were considered ≥CR2. Results Twenty three patients were identified; the median age was 51 (range: 17-71) years. 10 (43%) patients were identified as low-risk, 11(47%) were high-risk at diagnosis, and risk status was unknown in 2 patients. At the time of diagnosis 5(22%) patients had stage I-II disease, 17 (74%) patients had stage III-IV disease. Four (17%) patients had BM involvement at presentation and 1 had CNS disease. CODOX-M/IVAC-rituximab (2-4 cycles) was the most common first-line chemotherapy regimen (n = 10; 43%). Eight (34.7%) patients achieved CR1, 6 (26%) patients attained CR2 and 9 (39%) patients had a PR or refractory disease after more than 2 lines of chemotherapy. Median time to relapse from diagnosis was 8 months (IQR was 4-78). Median time from diagnosis to HCT was 7 months (IQR 5-9). 22 patients underwent autologous HCT with BEAM conditioning; 8 in CR1, 5 in CR2 and 9 in PR. One patient underwent matched sibling donor allogeneic HCT in CR2. The median follow up for the entire cohort was 35 months (IQR 4-92). Median PFS calculated from D0 of HCT to disease progression, last follow up or death was not reached (NR) for patients in CR1 and CR2, and 6 months in the PR cohort (p = 0.05). Median OS was not reached in patients who were in CR1 and CR2 as compared to 19 months in partial responders (p=0.055). Conclusion In our limited series, autologous HCT in CR1 is associated with an excellent outcome. About 50% of chemo sensitive patients in CR2 can also achieve long term remission after HCT. This finding needs to be validated in a larger cohort.

Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study

BackgroundTNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory molecule that plays a key role in active inflammation of lupus nephritis (LN). Urine TWEAK (uTWEAK) levels were found to be...

Bicalutamide 150 mg as secondary hormonal therapy for castration-resistant prostate cancer.

This study was aimed to evaluate the effect and tolerability of bicalutamide 150 mg therapy in patients with castration-resistant prostate cancer (CRPC). A total of 48 patients with histologically confirmed prostate cancer were included. They had been treated with continuous maximal androgen blockade therapy, but their serum prostate-specific antigen (PSA) increased after initial hormonal therapy. Patients were given bicalutamide (150 mg per day). Serum PSA testing was performed every 3 months. The response was defined according to PSA decline from baseline: PSA decline ≥85% as complete response, ≥50 % but <85% as partial response, and <50 % as failure. Response duration was defined as the time from PSA response until PSA increased ≥25 % or ≥2 ng/mL from the nadir. The potential predictive factors (Gleason score, clinical stage and serum PSA) were investigated. The time of follow-up was 3-30 months. A PSA decline ≥50% was observed in 37 of 48 patients including 18 ≥ 50% but <85% and 19 ≥ 85% responders. The median response duration was 12 months for partial responders and 20 months for complete responders. Patients with lower Gleason score, lower serum PSA and using flutamide as first-line nonsteroidal antiandrogen achieved more benefits. Moreover, bicalutamide 150 mg therapy was well tolerated. Bicalutamide 150 mg therapy was an appropriate therapeutic method for patients of CRPC, especially for those with lower Gleason score, lower serum PSA and using flutamide as first-line nonsteroidal antiandrogen.

Single‐agent lenalidomide is active in patients with relapsed or refractory aggressive non‐Hodgkin lymphoma who received prior stem cell transplantation

Patients with aggressive non-Hodgkin lymphoma (NHL) who relapse after autologous stem cell transplantation (ASCT) have a poor prognosis. Additional therapy is often poorly tolerated, and new treatment modalities are needed. This efficacy and safety study was a retrospective analysis of two phase II trials (NHL-002 and NHL-003) that studied single-agent lenalidomide in patients with relapsed/refractory aggressive NHL with prior (n = 87) compared with no prior ASCT (n = 179). The overall response rate in the ASCT group was 39% [14% complete response (CR)], including 29% in patients with diffuse large B-cell lymphoma, 63% in mantle cell lymphoma, and 60% in transformed lymphoma. The timing of transplant relative to receiving lenalidomide had no effect on outcomes. Median progression-free survival for the ASCT group was 3·7 months (16·9 months for patients in CR; 7·3 months for partial responders) at a median 12·5-month follow-up. Median response duration was 7·9 months. Regardless of prior ASCT, lenalidomide monotherapy was efficacious in heavily pretreated patients with aggressive, relapsed/refractory NHL, with a safety profile that was consistent with prior studies of single-agent lenalidomide.

Chemotherapy for the treatment of oligodendroglial tumors

Oligodendroglial tumors include the highly chemosensitive oligodendroglioma and mixed oligoastrocytoma. Patients with these tumors have a longer median survival and time to disease progression than patients with other brain tumor types, but the range is wide and the disease is inevitably fatal. Because of their chemosensitivity and the potential for radiation toxicity, lowgrade oligodendroglioma are increasingly being treated with adjuvant or neoadjuvant chemotherapy before radiation therapy. Approximately two thirds of patients with the more aggressive form (anaplastic oligodendroglioma) have shown substantial response to first-line procarbazine/lomustine/vincristine (PCV) therapy. However, experience with chemotherapy for relapse of disease following PCV therapy is limited. Several small trials have shown the safety and activity of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) in oligodendroglioma, regardless of prior PCV therapy. An open-label, phase II trial of temozolomide in 47 patients with relapsed oligodendroglioma showed an objective response rate of 43%, of which seven (15%) were complete responses. Median progression-free survival was 6 months and 34% of patients were disease-free at 12 months. Median survival was 26 months for complete responders and 11 months for partial responders. Temozolomide was well tolerated. The only grade 3/4 toxicity with temozolomide treatment was thrombocytopenia, which occurred in ≤ 5% of the 382 treatment cycles administered. The encouraging results of ongoing trials with temozolomide suggest the potential for its use as a first-line therapy in this patient population.

Response to chemotherapy is a major parameter-influencing long-term survival of metastatic breast cancer patients

In cancer patients, correlation between response to chemotherapy and gain in survival remains debated. We addressed this question in a multivariate analysis evaluating response to chemotherapy as a factor influencing survival of patients with metastatic breast cancer. From 1977 to 1992, 1430 patients included in eight consecutive prospective trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, were available for assessment. Median follow-up was 155 months. Median survival from the date of randomisation was 24 months. Objective response rate was 63.6%. A complete response (CR) was achieved in 17% (249 patients). In a stepwise forward progression analysis objective response was the first independent prognostic factor for survival. Median survival time was 43 months for complete responders (CR), 29 months for partial responders (PR), 18 months for stable disease (SD), 5 months for progressive disease (PD). The probability of survival at 5 and 10 years was 35% and 15% for CR's and decreased to 18% and 6% for PR's. The timing of best response (at 4 or 8 months) was not related to outcome. Response to an anthracycline-based chemotherapy is a major independent prognostic factor in metastatic breast cancer. The use of this factor to investigate new drugs seems to be pertinent. The good prognosis of complete responders justifies further evaluation of new treatment strategies for this patient population.

Phase I/II Trial of Etoposide and Carboplatin in Extensive Small-Cell Lung Cancer

Previously untreated extensive small-cell lung cancer (SCLC) patients with performance status 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and carboplatin doses of 50, 100, or 125 mg/m2/day on days 1-3 in a Phase I format. Among the ten eligible patients treated with 125 mg/m2/day of carboplatin, grade 3 or 4 infection occurred in six patients, grade 4 thrombocytopenia in four patients, and there was one death with myelosuppression. Thus, this dose was considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted utilizing this treatment program. In the Phase II trials, 81% of the 48 eligible patients had grade 3 or 4 leukopenia, 76% had grade 3 or 4 thrombocytopenia, and 55% had grade 3 or 4 anemia. There were three (6%) toxic deaths from myelosuppression. The objective response rate was 63% (17% complete responders) with a median response duration of 6.2 months for complete responders and 6.4 months for partial responders. Median survival was 12 months. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 25% increase in carboplatin compared to prior studies. Cancer and Leukemia Group B (CALGB) plans to study further dose intensification of this regimen with colony-stimulating factors.

No response or survival improvement in small cell lung cancer after sequential chemotherapy with three non-cross resistant drug regimens — a pilot study

In a pilot phase II study we have treated 25 patients with small cell lung cancer by utilizing 3 non-cross resistant drug regimens given in a sequential fashion in combination with radiotherapy to the primary tumor. VAC regimen (etoposide, doxorubicin, cyclophosphamide) was planned to induce major cytotoxity, CVM (cisplatin, vincristin, high-dose methotrexate) to intensify cell killing and MCP (mitomycin-C, CCNU, procarbazine) to maintain response. Overall response rate was 88% with 24% complete and 64% partial responders. Duration of response was 8.3 + months. Median survival was 12 months, 17 for complete and 10.5 months for partial responders. Sixty-one per cent survived for more than one year, while one patient is alive with no evidence of disease 30 months after diagnosis. In conclusion, sequential chemotherapy with non-cross resistant cytostatic agents in small cell lung cancer did not offer superior results compared to any other form of treatment.

Ifosfamide. Methotrexate and 5-Fluorouracil for Pretreated Advanced Breast Cancer

A total of 51 fully evaluable patients with advanced and intensively pretreated breast cancer were treated with a combination chemotherapy of ifosfamide plus mesna, methotrexate and 5-fluorouracil. All patients had received at least one series of combined chemotherapy, 30 patients had received more than one combination and 41 patients had had anthracyclines before. Metastatic lesions in more than one site were found in 42 patients, and 24 patients had metastatic liver lesions. Partial remission was achieved in 10 patients (20%) and no change in 16 patients (31%). Survival was almost identical in both groups of responding patients and significantly shorter in treatment failures. Response was favorable in patients without pretreatment with anthracyclines. Two patients who received this protocol directly after progression with cyclophosphamide, methotrexate and 5-fluorouracil (CMF protocol) responded with a partial remission. Median time to progression was 7 months for partial responders and 4.5 months for patients achieving a no-change status. Median survival was 8 months for all patients. Toxicity was tolerable. Leukocytopenia and thrombocytopenia were treatment-limiting parameters. Overall, this protocol is well tolerable and effective in breast cancer patients with advanced disease and in intensively pretreated patients.

Salvage chemotherapy for non Hodgkin's lymphoma of unfavourable histology with a combination of ccnu and vinblastine

Twenty patients with relapsed or refractory, intermediate or high grade non Hodgkin's lymphoma were treated with a combination of CCNU and vinblastine. Complete responses occurred in four patients (20 per cent), partial responses in eight (40 per cent), for an overall response rate of 60 per cent. The regimen was more effective in patients with high grade lymphoma, absence of constitutional symptoms, better response to prior treatment. Duration of response was 4, 8, 16, 30 months for complete responders; 2, 2, 6, 6, 6, 8, 9, 14 months for partial responders. This combination regimen seems at least as effective as most of other regimens utilized in salvage treatment of non Hodgkin's lymphomas, with a very acceptable toxicity.

Lymphoblastic lymphoma in adolescents and adults. Clinical, pathological and prognostic evaluation

Sixty-four adult patients with lymphoblastic lymphoma (LB) identified according to Kiel Classification were analyzed retrospectively. Three distinct clinical presentations were identified: prevalent abdominal disease ( 29 pts = 45.3%), prevalent mediastinal disease ( 14 pts = 21.9%) and prevalent superficial node involvement ( 21 pts = 32.8%). On histological grounds, the patients with abdominal disease were mainly associated to “Burkitt like” cell lymphoma ( 55%); patients with mediastinal disease to convoluted cell type ( 58%); and those with superficial node disease to unclassified cell type ( 48%). Immunological studies showed a significant correlation between mediastinal disease and T phenotype ( P = 0.0011), abdominal disease and B phenotype ( P = 0.00042), and between superficial node disease and non-B non-T phenotype ( P = 0.00024). Survival was independent of the type of clinical presentation and protocol employed but was correlated with the stage ( P < 0.0005), symptoms ( P < 0.025), bulky disease ( P < 0.025) and bone marrow involvement ( P < 0.025). Furthermore the response to therapy was strongly correlated with prognosis ( P < 0.0001) with 34.5 months median survival for complete responders, 9 months for partial responders, and 3 months for non-responders. Four patients underwent bone marrow transplantation (three autologous and one allogeneic BMT in a patient in leukemic phase); three of them are still in CR ( 18, 22 and 27 months from the transplant) while one patient had an early relapse and died 3 months later.

肺癌の診断と治療に関する研究

One hundred and thirteen patients with advanced lung cancer were treated with a four-drug combination chemotherapy consisting of cyclophosphamide, vincristine, methotrexate and procarbazine. Of those, ninety three (80 men and 13 women) patients were evaluated.Of 41 patients with small cell carcinoma, 10 (24%) achieved complete response (CR) and 18 (44%) achieved partial response (PR). The median duration of response was 5 months. The median survival time from initiation of chemotherapy was 11.3 months for patients with limited disease and 8 months for those with extensive disease. Responders lived significantly longer than non-responders; median survival time was 14 months for complete responders, 10.3 months for partial responders, and 6 months for non-responders.Of 52 patients with non-small cell carcinoma, 2 achieved CR and 15 achieved PR: The overall response rate was 33%; with a response rate of 30% (8/27) for adenocarcinoma, 30% (6/20) for squamous cell carcinoma, and 60% (3/5) for large cell carcinoma. The median survival time was 13 months for patients with stage III, and 8 months for those with stage IV. Responders with non-small cell carcinoma displayed a tendency toward longer survival periods; the median survival time was 8.3 months for responders compared with 6 months for non-responders.Myelosuppressive toxicity remained within acceptable limits, with 8.8% incidence of leucocytepenia (1, 000/cmm) and 6.7% incidence of thromobocytepenia (50, 000/cmm) in repeated courses. These resuts indicate that this regimen is useful for the treatment of advanced lung cancer.

Treatment of advanced bladder cancer using cis-platinum.

Cis-platinum (120 mg/m2) was given to 14 patients with locally inoperable or metastatic transitional cell carcinoma of the bladder. Five patients (35%) showed a response, two complete (14%), and three partial (21%). Nine patients (65%) had no response. The median duration of survival was 3.5 months for non-responders; 6.5 months for partial responders; and 25 months for complete responders. The side effects and implications of treatment using this agent are discussed.

Combination chemotherapy for small cell carcinoma of the lung: evaluation of four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine.

Forty-one patients with small cell carcinoma of the lung were treated with a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine. The response rate was 68% (28 responded among 41 patients), with 10 complete responses (24%) and 18 partial responses (44%). The median survival time from the initiation of chemotherapy was 11 months for patients with limited disease and 8 months for those with extensive disease. Patients who achieved complete response survived significantly longer than those who did not; the median survival time for complete responders was 14.5 months, compared to 8.5 months for partial responders and 6 months for non-responders. Myelosuppressive toxicity remained within acceptable limits, with 5% incidence of leukocytopenia (less than 1,000/microliter) and 7% incidence of thrombocytopenia (less than 50,000/microliter) following the first course of the regimen.

Treatment of metastatic brain tumors with the combination of 1-methyl-1-nitrosourea (MNU) and cyclophosphamide.

The combination of MNU and cyclophosphamide was applied in 29 consecutive previously untreated patients with metastatic brain tumors. An objective regression of the metastatic process in the brain, with seven complete and seven partial remission, was observed in 14 out of 29 patients (48%). In three patients the disease was stable, and in 12 it progressed in spite of treatment. The objective parameters used in monitoring the effect of therapy included brain scintiscan, computerized brain tomography and neurological clinical status. Median remission duration was 11.2 months in complete responders, and 5.6 months in partial responders. Median survival was also the longest in complete responders (15.7 months). The median survival of non-responding patients was only 3.1 months.

Combination Chemotherapy with Adriamycin, Cyclophosphamide, Methotrexate and Vincristine in Lung Cancer Patients with Extensive Disease

The combination of adriamycin, cyclophosphamide, methotrexate and vincristine was applied in 38 patients with extensive lung cancer. Sixteen patients had previously undergone radiotherapy, while 22 patients had not been previously treated. The group included 22 squamous cell carcinomas, 12 small-cell carcinomas, 3 adenocarcinomas and 1 large-cell carcinoma. In terms of the performance status, 39% of the patients were in grade 7-5 (Karnofsky scale) and 61% in grade 4-2 group, i.e., the majority of the patients were, chemotherapy-wise, a high risk group. Two complete and 7 partial remissions were achieved, with a response rate of 24%. In terms of histological type, 1 complete and 4 partial remissions were achieved in the 12 treated small-cell carcinoma patients (response rate 42%). In the non-small-cell carcinoma group, the response rate was 17%, but the difference in response was statistically significant only as compared with squamous cell carcinoma (p &lt; 0.05). Previous radiotherapy influenced the results of treatment, but not to an extent which would be statistically significant (p &gt; 0.05). The duration of the remissions was 10 to 18 months in complete responders; the median remission duration was 6.5 months in partial responders and 3 months in stable disease cases. The median survival of responders and non-responders showed a pronounced difference (10.8 months versus 2.2 months). The highest response was obtained in lymph node metastases (44%), the primary tumor (24%), and cutaneous and subcutaneous metastases (20%). Metastases in the liver, lungs and particularly the bones and brain were resistant to therapy. Toxic changes were evident, and therapy had to be discontinued in 5 patients for a longer or shorter time because of myelosuppression. However, no heart failures or drug-related deaths were observed. The study has shown that this combination of cytostatic drugs, even in patients with extensive lung cancer, can be expected to produce a response in about one-fourth of treated patients and an even higher response in small-cell carcinoma and previously non-irradiated cases.

Prednimustine (NSC-134087, leo 1031) treatment of lymphocytic and lymphocytic-histiocytic lymphomas

Nineteen patients with advanced lymphocytic or lymphocytic-histiocytic lymphomas were treated with Prednimustine (NSC-134087, Leo 1031). The median induction dose was 25 mg/m2 a day by mouth (range 11-42). Ten patients had previously received radiation or chemotherapy, or both. Four patients had a complete remission and eleven a partial remission. The median duration of remission was 12.5+ months for complete responders and 5 months for partial responders. Thirteen patients had a moderate myelosuppression. One patient had urticaria and pruritus and refused further treatment.