bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasminogen activator inhibitor-1 and prognosis in primary breast cancer.
Authors: Foekens J A , Schmitt M , van Putten W L , Peters H A , Kramer M D , Jänicke F , Klijn J G
Published: February 2017

PURPOSE

Evaluation of the relationship between plasminogen activator inhibitor-1 (PAI-1) and the metastatic potential of primary breast cancer, and to compare the prognostic impact of PAI-1 in multivariate analysis with those of conventional prognostic factors, including steroid-hormone receptors, and those of urokinase plasminogen activator (uPA), pS2-protein (PS2), and cathepsin D.

PATIENTS AND METHODS

Cell biologic prognostic factors were analyzed in 657 cytosols routinely prepared from frozen-tissue biopsies that were submitted to our laboratory for the assessment of steroid-hormone receptor status. The median duration of follow-up in patients still alive at the time of analysis was 48 months. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assay, PS2, and cathepsin D by radiometric immunoassay, and uPA and PAI-1 by enzyme-linked immunosorbent assay (ELISA).

RESULTS

PAI-1 levels were found to be strongly positively correlated with the rates of relapse (P < .0001) and death (P < .001). Relating the levels of PAI-1 with those of other cytosolic prognostic factors, we found a positive association with the metastasis-related proteases uPA (P < .0001) and cathepsin D (P < .0001). On the other hand, PAI-1 levels were found to be negatively correlated with ER (P < .005) and PgR (P < .001), and the estrogen-regulated pS2-protein (P < .001), which are proteins associated with a favorable prognosis. In multivariate regression analysis for 5-year relapse-free survival, and using an optimized cutoff point for discrimination between PAI-1-positive and -negative, independent predictors of the rate of relapse were found to be PAI-1 (P < .0001) and uPA (P = .01) of the cytosolic parameters, and tumor size, lymph node status, and premenopausal age of the clinical parameters. In multivariate analysis in patients with node-negative disease, only PAI-1 (P < .001) and tumor size (P = .03) were positively and premenopausal age negatively (P < .001) associated with the rate of relapse. In patients with node-positive disease, PAI-1 (P < .001), uPA (P = .02), tumor size (P < .001), and the number of positive lymph nodes (P < .001) were all positively associated with the rate of relapse.

CONCLUSION

We conclude that the PAI-1 level measured in routinely prepared cytosols is an important parameter to predict the metastatic potential in both node-negative and node-positive human primary breast cancer.
Leukemia: management of relapse after allogeneic bone marrow transplantation.
Authors: Kumar L
Published: February 2017

PURPOSE

To review the current state of knowledge regarding the management of leukemic relapse after allogeneic bone marrow transplantation (BMT).

PATIENTS AND METHODS

The literature was analyzed using MEDLINE (National Library of Medicine, Bethesda, MD) and reports were identified through review of report bibliographies. Pertinent studies were selected and data synthesized into a review format.

RESULTS

Leukemic relapse after allogeneic BMT is an important cause of treatment failure. The risk of leukemic relapse varies from 20% to 60% depending on the diagnosis and phase of disease. Reinduction chemotherapy (CT), second BMT, interferon (IFN) alfa, and donor leukocyte infusions are various options, but none of the approaches is clearly optimal. Approximately 50% of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients achieve remission after standard induction CT. However, most patients finally relapse and die of uncontrolled leukemia. Second BMT is successful in 20% to 25% patients and is a reasonable option in patients who relapse more than 6 months after the initial transplant. Young patients with a good performance status and those in remission from initial transplant relapse have a better outcome after second BMT. Venocclusive disease (VOD), interstitial pneumonitis (IP), and acute graft-versus-host disease (GVHD) are the main complications. Therapy with IFN alfa results in cytogenetic complete remission (CR) in 10% to 25% patients with chronic myeloid leukemia (CML). The initial results of leukocyte infusions from the original donor are promising. However, acute GVHD and bone marrow aplasia are associated complications. The correct dose and schedule of donor leukocyte infusions need to be determined in future studies to minimize GVHD while maintaining the graft-versus-leukemia (GVL) effect.

CONCLUSION

Identification of patients at increased risk for relapse and use of biologic response modifiers post-transplant to augment the GVL effect in such patients are possible areas of improvement for future studies.
Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.
Authors: Thigpen J T , Blessing J A , Ball H , Hummel S J , Barrett R J
Published: February 2017

PURPOSE

This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy.

PATIENTS AND METHODS

Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol.

RESULTS

Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each.

CONCLUSION

Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.
Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.
Authors: Wishart G C , Bissett D , Paul J , Jodrell D , Harnett A , Habeshaw T , Kerr D J , Macham M A , Soukop M , Leonard R C
Published: February 2017

PURPOSE

To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer.

PATIENTS AND METHODS

Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses.

RESULTS

Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63).

CONCLUSION

Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.
Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report.
Authors: Hussain M , Wolf M , Marshall E , Crawford E D , Eisenberger M
Published: February 2017

PURPOSE

To assess the impact of prognostic factors, including continued (orchiectomy) versus discontinued androgen-suppression (nonorchiectomy) therapy, on chemotherapy response and survival of patients with hormone-refractory prostate cancer.

METHODS

Analysis of five consecutive Southwest Oncology Group (SWOG) phase II chemotherapy trials was undertaken.

RESULTS

Two hundred five hormone-refractory patients were evaluated. Eighty-four percent had been orchiectomized. The median survival durations for the nonorchiectomy and orchiectomy patients were 6 and 7 months, respectively (P = .73). In a univariate analysis, orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy (1.1 v 0.1 years, P = .003), were more likely to have had chemotherapy initiated > or = 2 years from diagnosis (75% v 56%, P = .03), had a lower incidence of liver metastases (16% v 30%, P = .05), and had lower likelihood of being black (8% v 18%, P = .05) when compared with the nonorchiectomy group. Orchiectomy patients had a marginally significant longer median time from initial hormone treatment, more prior endocrine manipulations, lower median baseline alkaline phosphatase levels, and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group. Absence of liver metastases (P = .004), hemoglobin level > or = 10 g/dL (P < .001), acid phosphatase level > or = 1.2 IU/L (P = .05), response to chemotherapy (P = .001), and > or = 2 years from initial hormone treatment (P = .01) are important factors for survival.

CONCLUSION

This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression. A prospective randomized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy.
Improved survival for patients with AIDS-related Kaposi's sarcoma.
Authors: Miles S A , Wang H , Elashoff R , Mitsuyasu R T
Published: February 2017

PURPOSE

We retrospectively analyzed all patients with AIDS-related Kaposi's sarcoma (AIDS-KS) seen at one large California medical center to delineate factors that may have contributed to a relative decline in survival.

METHODS

Potential prognostic factors were analyzed individually, using the Cox proportional hazards regression model, for their association with survival. After a stepwise Cox regression procedure was applied to those factors that showed a significant effect on survival, a subset of factors that best predicted survival was identified. We then quantified the effect of the year of diagnosis on survival using a univariate Cox model. Next, we combined the year of diagnosis with the subset of prognostic factors previously identified into the Cox model to examine survival after adjustment for the prognostic factors. Survival distribution was estimated by the Kaplan-Meier method, and the 95% confidence interval for the median survival was computed using the modified reflected method.

RESULTS

In 688 patients, we identified four baseline variables that best predicted survival: CD4 cell number, hematocrit, number of KS lesions, and body mass index (BMI). Adjusted for these predictive factors, there was a significant improvement in survival for patients with AIDS-KS over the last 6 years.

CONCLUSION

Contrary to prior reports, survival has increased for patients with AIDS-KS. The apparent increase in observed mortality is most likely due to a decline in the CD4 cell number at presentation.
Effect of body position on ventricular CSF methotrexate concentration following intralumbar administration.
Authors: Blaney S M , Poplack D G , Godwin K , McCully C L , Murphy R , Balis F M
Published: February 2017

PURPOSE

Intralumbar methotrexate is one of the primary therapeutic modalities for the prevention and treatment of meningeal leukemia. However, methotrexate distribution to the ventricles is limited and highly variable following intralumbar dosing, and cytotoxic concentrations of methotrexate are not always achieved or sustained in the ventricular CSF. We used a nonhuman primate model to determine the effect of body position on the caudal distribution of an intralumbar dose of methotrexate.

METHODS

Methotrexate (1.0 mg) was administered by intralumbar injection to four animals, which were then immediately placed either in an upright sitting position or in a prone position for 1 hour, then upright. Each animal served as its own control and was studied in each position on at least one occasion.

RESULTS

The mean peak ventricular methotrexate concentration was 0.12 mumol/L (range, 0.091 to 0.20) in animals that were immediately placed upright, compared with 2.81 mumol/L (range, 0.21 to 8.9) in animals that remained prone for 1 hour. The mean area under the concentration-versus-time curves (AUC) was 0.51 mumol/L.h (range, 0.26 to 1.1) in the upright animals and 12.0 mumol/L.h (range, 0.9 to 35.4) in the prone animals.

CONCLUSION

Maintaining a prone position for 1 hour after an intralumbar dose increased the peak methotrexate concentration and drug exposure in ventricular CSF. CSF drug distribution following intralumbar therapy can be influenced by body position after the injection.
Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries.
Authors: Bunt A M , Hermans J , Smit V T , van de Velde C J , Fleuren G J , Bruijn J A
Published: February 2017

PURPOSE

Possible causes underlying the substantial differences in gastric cancer survival rates observed between Japan and the West were examined in a randomized trial comparing the Western R1 resection with limited lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy.

PATIENTS AND METHODS

The effect of four factors associated with lymphadenectomy on microscopic tumor-node-metastasis (TNM) staging, and on stage-specific survival rates was assessed in 473 curatively resected patients.

RESULTS

After application of extended lymphadenectomy, additional information on N status was available, only in R2 resections with up-staging to N2 status in 30% of patients. The calculated effect of this stage migration on known 5-year survival rates was as follows: an increase of 1% in TNM stage Ia, 2% in Ib, 7% in II, 15% in IIIa, and 15% in IIIb. A further increase in survival was observed by stage migration to N3 or N4 status, due to selective extension of lymphadenectomy to clinically overt metastases located outside the allocated level of clearance (contamination). Incomplete lymphadenectomy of N1- or N2-level stations indicated for dissection (noncompliance) demonstrates that more migration can occur when strictly adhering to the protocol. Examining more nodes per N level (diligence) induces even more migration, since the number of nodes that were histologically examined per N level correlated significantly with nodal status (lymph node-negative [N-] or lymph node-positive [N+]).

CONCLUSION

These factors explain, at least partially, superior stage-specific survival rates after R2 compared with R1 resections, without a real survival benefit in individual patients.
Complications of indwelling venous access devices in cancer patients.
Authors: Eastridge B J , Lefor A T
Published: February 2017

PURPOSE

We undertook this study to review our experience with indwelling vascular access devices in cancer patients to identify factors associated with complications.

PATIENTS AND METHODS

A total of 322 indwelling devices were placed in 274 cancer patients by a single surgeon. Devices were placed via percutaneous insertion in 72% (231 of 322) and via venous cutdown in 28% (91 of 322). We placed external catheters in 209 of 322 patients (65%) and subcutaneous infusion ports in 113 of 322 (35%).

RESULTS

Pneumothorax occurred in four of 231 (1.7%) of the percutaneously placed devices. Postoperative complications included sepsis and thrombosis, which necessitated premature removal of the devices. Device related sepsis occurred in 28 of 209 patients (13%) with catheters and six of 113 patients (5%) with subcutaneous ports. Thrombosis occurred in 21 of 209 patients (10%) with catheters and seven of 113 (6%) with subcutaneous ports. In 15 of 19 devices removed for thrombosis, the tip was above the T3 level. Seventeen devices were placed in the saphenous vein, with a complication rate similar to that observed in upper-body devices.

CONCLUSION

We found a significantly (P < .05, chi 2 analysis) increased incidence of thrombotic complications in patients with triple-lumen catheters (10 of 48) compared with double-lumen catheters (11 of 160), as well as a significantly (P < .05) decreased mean time until catheter failure (40 v 146 days). We also observed a significant increase in the rate of thrombosis in patients with a catheter tip above the T3 level. We therefore recommend the use of fluoroscopy at the time of placement to assure adequate catheter length and tip position and the use of triple-lumen catheters only when necessary for concurrent drug administration.
High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial.
Authors: Bezwoda W R , Seymour L , Dansey R D
Published: February 2017

PURPOSE

The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival.

PATIENTS AND METHODS

Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable.

RESULTS

The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy.

CONCLUSION

HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.
Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.
Authors: Waber D P , Tarbell N J , Fairclough D , Atmore K , Castro R , Isquith P , Lussier F , Romero I , Carpenter P J , Schiller M
Published: February 2017

PURPOSE

We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy.

PATIENTS AND METHODS

Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue.

RESULTS

There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001).

CONCLUSION

We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.
Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.
Authors: Hammel P , Haioun C , Chaumette M T , Gaulard P , Divine M , Reyes F , Delchier J C
Published: February 2017

PURPOSE

The treatment of low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma with prominent gastric expression is controversial. Total gastrectomy has been proposed, but is associated with significant morbidity. The aim of this monocentric study was to assess the efficacy of continuous oral chemotherapy with a single alkylating agent.

PATIENTS AND METHODS

Twenty-four consecutive patients, 13 men and 11 women, were studied. Their mean age was 51 years (range, 22 to 79). Low-grade B-cell MALT lymphoma was diagnosed by histologic and immunohistologic examination of endoscopic biopsies. Seventeen patients had stage I disease and seven stage IV disease, with lung and gastric involvement. Two of these seven patients also had bone marrow involvement. The alkylating agent (cyclophosphamide or chlorambucil) was administered orally and daily for periods of 12 to 24 months.

RESULTS

The median follow-up time was 45 months (range, 14 months to 14 years). Complete remission was obtained in 18 patients (75%) after a median treatment duration of 12 months. Five patients relapsed; two of them were successfully re-treated, and one died of MALT lymphoma that had transformed into large-cell lymphoma. Chemotherapy was stopped after 24 months for six patients who only achieved a partial remission; two of them required further treatment for progressive disease (surgery for a small-bowel localization in one case and cyclophosphamide rechallenge in the other). Nine patients had neutropenia that required a reduced chemotherapy dosage.

CONCLUSION

In low-grade MALT lymphoma with prominent gastric expression, continuous monochemotherapy may constitute an efficient alternative to gastrectomy, regardless of disease stage.
Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.
Authors: Bui B N , Chevallier B , Chevreau C , Krakowski I , Peny A M , Thyss A , Maugard-Louboutin C , Cupissol D , Fargeot P , Bonichon F
Published: February 2017

PURPOSE

This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy.

PATIENTS AND METHODS

Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner.

RESULTS

Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles.

CONCLUSION

Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.
Coherent view of non-Hodgkin's lymphoma.
Authors: Aisenberg A C
Published: February 2017

PURPOSE

Even though non-Hodgkin's lymphoma is already sixth in incidence and mortality among malignant neoplasms (and the incidence was increasing at a rate of 3% to 4% per year before the advent of AIDS epidemic-associated lymphomas), most physicians and many oncologists find the disorder arcane. The problem lies in the complexity of human lymphoma, which encompasses more than a dozen neoplasms of the lymphoid system. The goal of this review is to provide user-friendly access to the condition.

METHODS

The variety of inputs required for a subdivision of non-Hodgkin's lymphoma that is useful to clinicians includes lymphocyte lineage and sublineage based on microscopic appearance and immunophenotype, clinical behavior manifest in survival and early dissemination, and analysis of molecular genetic and cytogenetic abnormalities, which reflect pathogenic oncogene derangements. Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-1) are important in certain uncommon lymphomas.

RESULTS AND CONCLUSION

The subtypes of primary B-lineage nodal lymphoma include low-grade (small lymphocytic, lymphoplasmacytic-lymphoplasmacytoid, follicular small cleaved cell, and follicular mixed small cleaved and large cell), intermediate-grade (follicular large cell, diffuse small cleaved or mixed, and intermediate lymphocytic), and high-grade (diffuse large cell, immunoblastic, and small noncleaved cell) neoplasms. The less common lymphomas of T lineage and lymphomas that arise in extranodal sites are placed in separate subdivisions. This subdivision serves as a guide to prognosis and treatment.
Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.
Authors: Weber B L , Vogel C , Jones S , Harvey H , Hutchins L , Bigley J , Hohneker J
Published: February 2017

PURPOSE

We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed.

PATIENTS AND METHODS

A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study.

RESULTS

The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis.

CONCLUSION

Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.
Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults.
Authors: Kushner B H , Meyers P A , Gerald W L , Healey J H , La Quaglia M P , Boland P , Wollner N , Casper E S , Aledo A , Heller G
Published: February 2017

PURPOSE

To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV).

PATIENTS AND METHODS

This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy.

RESULTS

Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy.

CONCLUSION

Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.
Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer.
Authors: Moertel C G , Fleming T R , Macdonald J S , Haller D G , Laurie J A , Tangen C M , Ungerleider J S , Emerson W A , Tormey D C , Glick J H
Published: February 2017

PURPOSE

To determine the effectiveness of fluorouracil plus levamisole administered postoperatively to patients with resected stage II (Dukes' B2) colon cancer.

PATIENTS AND METHODS

This randomized controlled clinical trial (INT-0035) was performed by National Cancer Institute-sponsored cancer clinical trials cooperative groups. Patients were assigned to observation only or to fluorouracil (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side effects were assessed.

RESULTS

Three hundred eighteen eligible patients were analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole reduced the recurrence rate by 31%, although this trend was not statistically significant (P = .10). A total of 87 patients died: 43 on observation and 44 on fluorouracil plus levamisole. Disparity between effects on recurrence rate and overall survival is partially explained by a higher rate of non-colon cancer-related deaths on fluorouracil plus levamisole (15 v seven) and by the effects of salvage surgery with curative intent. Of seven patients with recurrence who were rendered disease-free by salvage surgery, six were on the observation arm. As was observed in patients treated with fluorouracil plus levamisole for stage III disease, toxicity was acceptable and compliance was excellent.

CONCLUSION

Fluorouracil plus levamisole is tolerable and accepted as standard surgical adjuvant therapy for patients with stage III colon cancer, but the data from this study in stage II patients suggest a decreased relapse rate without a significant improvement in survival.
Evaluation of the efficacy of the VEEP regimen in adult Hodgkin's disease with assessment of gonadal and cardiac toxicity.
Authors: Hill M , Milan S , Cunningham D , Mansi J , Smith I , Catovsky D , Gore M , Zulian G , Selby P , Horwich A
Published: February 2017

PURPOSE

The aim of this phase II study was to investigate the potential of the vincristine, epirubicin, etoposide, and prednisolone (VEEP) regimen to reduce the risks of long-term sequelae of chemotherapy such as sterility, cardiopulmonary damage, and second malignancies, while maintaining efficacy in terms of response and survival.

PATIENTS AND METHODS

Eighty-five adult patients with newly diagnosed and previously untreated stage II to IV Hodgkin's disease (HD) were entered and monitored for a minimum of 1 year. Patients were treated to maximum response plus two further courses, and if they had not attained a complete response (CR) or CR-unconfirmed/uncertain [CR(u)] were changed to second-line chemotherapy. Adjuvant radiotherapy was administered to patients with bulky disease and those with postchemotherapy residual masses. Measurements of left ventricular ejection fraction (LVEF), gonadotropins in females, and sperm count in males were taken both before and after treatment with VEEP.

RESULTS

The maximum rates of response were as follows: CR, 32%; CR(u), 47%; and PR, 21% [CR + CR(u), 79%]. The median follow-up duration is 45 months, with a 5-year overall survival (OS) rate of 89% and failure-free survival (FFS) rate of 62%. Patients in CR at the end of chemotherapy had a higher FFS at 5 years compared with patients in CR(u) (88% v 56%). Acute toxicity was mild, with no pulmonary toxicity or treatment-related deaths. The median LVEF was 62% before VEEP and 57% after VEEP. Gonadal function tests following treatment were normal in 92% of males and 100% of females. No second malignancies have been observed.

CONCLUSION

VEEP is an active combination with tolerable acute toxicity that preserves fertility and cardiopulmonary function. The efficacy of VEEP is comparable to that of established regimens, but a definitive evaluation of its potential to reduce second malignancies will require a longer follow-up duration.
Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.
Authors: Tattersall M H , Lorvidhaya V , Vootiprux V , Cheirsilpa A , Wong F , Azhar T , Lee H P , Kang S B , Manalo A , Yen M S
Published: February 2017

PURPOSE

Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial.

PATIENTS AND METHODS

Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy.

RESULTS

Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone.

CONCLUSION

Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.
Significance of normal serum prostate-specific antigen in the follow-up period after definitive radiation therapy for prostatic cancer.
Authors: Zelefsky M J , Leibel S A , Wallner K E , Whitmore W F , Fuks Z
Published: February 2017

PURPOSE

To determine the prognostic significance of a normal serum prostate-specific antigen (PSA) level in patients with prostatic cancer with long-term follow-up evaluation after radiotherapy.

MATERIALS AND METHODS

PSA information was available in 403 patients (38%) who were treated with pelvic lymph node dissection and retropubic radioactive iodine-125 implantation. One hundred eighty-two patients had a normal serum PSA level (< or = 4.0 ng/mL) the first time this test was conducted during the follow-up period, designated PSA-1.

RESULTS

Among patients with PSA-1 values < or = 1.0 ng/mL, the 5-year PSA relapse-free survival rate was 85% compared with 27%, respectively, among those with PSA values in the higher range of normal (P < .00001). Multivariate analysis demonstrated that only a PSA-1 value greater than 1.0 to < or 4.0 (P < .00001) and grade II/III histology (P = .009) had a negative impact on continued PSA relapse-free survival. The only independent variable identified by a multivariate analysis to affect local relapse-free survival (LRFS) was a PSA-1 value greater than 1.0 to < or = 4.0 ng/mL (P < .004), while high-grade histology (P < .0001) and local failure (P < .001) were the only significant variables to affect distant metastases-free survival (DMFS).

CONCLUSION

Patients with PSA values < or = 1.0 ng/mL are significantly less likely to have a subsequent relapse after therapy than those with levels greater than 1.0 to < or = 4.0 ng/mL. Continuously maintained PSA levels of < or = 1.0 ng/mL after treatment may serve as an end point for early evaluation of the efficacy of experimental radiotherapy protocols in prostate cancer.
Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial.
Authors: Loehrer P J , Johnson D , Elson P , Einhorn L H , Trump D
Published: February 2017

PURPOSE

This prospective, randomized trial was designed to determine if three cycles of cisplatin plus etoposide (PVP16) can produce therapeutic results comparable to three cycles of cisplatin, etoposide, and bleomycin (PVP16B) in patients with disseminated germ cell tumors.

PATIENTS AND METHODS

One hundred seventy-eight patients with minimal- or moderate-stage disease (Indiana staging system) were randomized to receive cisplatin (20 mg/m2 on days 1 to 5) plus etoposide (100 mg/m2 on days 1 to 5) with or without weekly bleomycin (30 IU/wk for 9 consecutive weeks). Following three cycles of chemotherapy over 9 weeks, patients with residual radiographic disease underwent surgical resection. If persistent carcinoma was noted, two additional 3-week courses of chemotherapy were administered.

RESULTS

One hundred seventy-one patients were fully assessable for response and survival. The two treatment groups were similar with respect to patient characteristics. The toxicities were comparable between the two arms. No clinically significant incidence of pulmonary toxicity occurred with PVP16B. Overall, 81 of 86 patients (94%) who received PVP16B and 75 of 85 patients (88%) who received PVP16 achieved a disease-free status with chemotherapy and/or surgery. However, greater numbers of treatment failures, including persistent carcinoma in postchemotherapy resected residual disease and relapses from complete remission, occurred on the arm without bleomycin (overall adverse outcome, P = .004). The failure-free (86% v 69%; P = .01) and overall survival (95% v 86%; P = .01) rates were inferior on the PVP16 arm.

CONCLUSION

Bleomycin is an essential component of PVP16B therapy in patients who receive three cycles of treatment for minimal- or moderate-stage disseminated germ cell tumors.
Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma.
Authors: Atzpodien J , Lopez Hänninen E , Kirchner H , Bodenstein H , Pfreundschuh M , Rebmann U , Metzner B , Illiger H J , Jakse G , Niesel T
Published: February 2017

PURPOSE

In a phase II multiinstitutional outpatient trial, patients with progressive metastatic renal cell carcinoma were treated with a combination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2 (rIFN alpha 2).

PATIENTS AND METHODS

One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m2 three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m2 three times per week in weeks 2, 3, 5, and 6. Additionally, patients received SC rIFN alpha 2 6 x 10(6) U/m2 once per week in weeks 1 and 4, and three times per week in weeks 2, 3, 5, and 6.

RESULTS

There were nine (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 months, respectively. Additionally, 55 patients (36%) had stable disease (SD). Fifty-nine patients (39%) had continued disease progression (PD) despite treatment, or went off study after less than 4 weeks of therapy. The majority of patients treated experienced fever, chills, malaise, nausea, vomiting, and anorexia, side effects that were mostly limited to World Health Organization (WHO) grade 1 and 2. However, one patient developed grade 4 CNS toxicity with extended somnolence. On cessation of therapy, the neurologic symptoms in this patient were fully reversible, with no neurologic deficiency.

CONCLUSION

In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demonstrated drastically reduced systemic toxicity, while it confirmed the therapeutic efficacy of the low-dose SC immunotherapy combination schedule.
High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy.
Authors: Demirer T , Weaver C H , Buckner C D , Petersen F B , Bensinger W I , Sanders J , Clift R A , Lilleby K , Anasetti C , Martin P
Published: February 2017

PURPOSE

To evaluate a high-dose chemotherapy regimen without total-body irradiation (TBI) followed by allogeneic (allo) bone marrow transplantation (BMT) in patients with lymphoid malignancies who had received prior dose-limiting radiotherapy.

PATIENTS AND METHODS

Fifty-six patients with non-Hodgkin's lymphoma (NHL, n = 26), Hodgkin's disease (HD, n = 17), or acute lymphoblastic leukemia (ALL, n = 13) with a history of previous radiation therapy were treated with cyclophosphamide (7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2; CBV) followed by allo BMT.

RESULTS

Nine of 56 patients are alive and disease-free a median of 1,091 (range, 512 to 1,784) days post-transplant. The probabilities of transplant-related mortality, relapse, and event-free survival at 2 years for the entire group of 56 patients were .62, .59, and .17, respectively. Patients who received 600 mg/m2 of carmustine had a higher incidence of grade 3 or 4 regimen-related toxicities (RRTs) (14 of 22) than did patients who received 300 mg/m2 (12 of 33; P < .04), whereas there was no difference in relapse (.34 and .53, respectively, P = .73). Fourteen of 16 patients who received allo BMT for advanced disease (n = 12) or less-advanced disease (n = 4) but who were also eligible for auto BMT relapsed (n = 4) or died of transplant-related complications (n = 10).

CONCLUSIONS

Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either allo or auto BMT was limited and precluded meaningful analysis of relative effectiveness.