bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous bone marrow transplant in acute myeloid leukemia in first remission.
Authors: Cassileth P A , Andersen J , Lazarus H M , Colvin O M , Bennett J M , Stadtmauer E A , Kaizer H , Weiner R S , Edelstein M , Oken M M
Published: February 2017

PURPOSE

The Eastern Cooperative Oncology Group conducted a prospective study of postremission high-dose chemotherapy and autologous bone marrow transplantation (autoBMT) in a group of uniformly treated adults with de novo acute myeloid leukemia (AML) to evaluate whether intensive, myeloablative therapy in first complete remission (CR) could improve the disease-free survival.

PATIENTS AND METHODS

After initial CR was induced by the combination of daunorubicin, cytarabine, and thioguanine, patients not eligible for allogeneic bone marrow transplantation (alloBMT) were offered autoBMT. Within a median of 2 months after CR, and without intervening postremission therapy, bone marrow was obtained, purged by exposure to 4-hydroperoxycyclophosphamide (4-HC), and cryopreserved. High-dose therapy consisted of oral busulfan over 4 days (16 mg/kg total) followed by intravenous (IV) cyclophosphamide 50 mg/kg daily for 4 days. The cryopreserved marrow was then reinfused.

RESULTS

Of the 39 patients scheduled for autoBMT, four relapsed before transplantation. Two of the 35 (6%) transplant patients died of transplant-related complications, and 11 (33%) relapsed a median of 8 months after marrow reinfusion. No relapse has occurred after 24 months posttransplant. With a median follow-up of 31 months, the median disease-free survival period for all 39 patients has not been reached; however, 54% +/- 16% of patients are projected to be alive and disease-free at 3 years.

CONCLUSION

Long-term, disease-free survival after autoBMT in AML seems to be better than the outcome after conventional-dose postremission therapy and rivals the results of alloBMT.
Surgical salvage of chemorefractory germ cell tumors.
Authors: Murphy B R , Breeden E S , Donohue J P , Messemer J , Walsh W , Roth B J , Einhorn L H
Published: February 2017

PURPOSE

Patients with disseminated germ cell tumors who relapse after salvage chemotherapy, or who progress during cisplatin-based therapy, have chemorefractory disease and a very poor prognosis. A subset of these patients will have chemorefractory but resectable disease. We have therefore evaluated the role of salvage surgery in this patient population.

PATIENTS AND METHODS

We performed a retrospective review of all patients with disseminated germ cell tumors who were felt to have chemorefractory disease and underwent salvage surgery from 1977 to 1990 at Indiana University. All patients had elevated serum markers or other signs of progressive carcinoma. A total of 48 patients underwent surgery (33 retroperitoneal lymph node dissections [RPLNDs], six thoracotomies, three thoracoabdominal resections, and multiple asynchronous procedures in six patients).

RESULTS

Thirty-eight of 48 patients (79%) were rendered grossly free of disease and 29 (60%) obtained a serologic remission. Ten patients (21%) remain continuously disease-free with no postoperative treatment with a median follow-up of 46 months (range, 31 to 89). Six additional patients who relapsed after salvage surgery are currently disease-free with further treatment (four with repeat surgery and two with high-dose chemotherapy and autologous bone marrow transplantation [ABMT]).

CONCLUSION

Selected patients with chemorefractory but resectable germ cell tumors have definite potential for cure with salvage surgery.
Randomized trial of hepatic arterial floxuridine, mitomycin, and carmustine versus floxuridine alone in previously treated patients with liver metastases from colorectal cancer.
Authors: Kemeny N , Cohen A , Seiter K , Conti J A , Sigurdson E R , Tao Y , Niedzwiecki D , Botet J , Budd A
Published: February 2017

PURPOSE

This study was designed to determine if hepatic arterial therapy with floxuridine (F), mitomycin, and carmustine (BCNU) (FMB) is superior to hepatic arterial therapy with F alone in previously treated patients with hepatic metastases from colorectal cancer.

PATIENTS AND METHODS

Ninety-five patients were randomized to intrahepatic FMB versus intrahepatic F. All patients had tumor progression after systemic chemotherapy (either therapeutic or adjuvant).

RESULTS

There was no significant difference in response rate (47% FMB v 33% F; P = .17). Median survival was similar in the two groups, 19.1 months for the FMB group compared with 14.0 months for the F group (P = .23). The overall median survival was 16.8 months. In patients who received prior adjuvant therapy, there was no difference between the two groups, but response rate was high in both (50% FMB v 62% F). The response rate for all patients who had received only prior adjuvant therapy versus all those who had received prior therapy for metastatic disease was 57% and 35%, respectively (P = .066). In the subset of patients whose disease had progressed with prior systemic chemotherapy, the response rate to FMB was greater than that to F (47% v 23%; P = .035).

CONCLUSION

The overall partial response rate of 39% and the overall survival of 16.8 months from initiation of intrahepatitis therapy show that hepatic arterial therapy is a reasonable treatment option for patients whose tumor does not respond to systemic therapy or whose disease progresses after adjuvant therapy for colorectal cancer.
Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial.
Authors: Hoover H C , Brandhorst J S , Peters L C , Surdyke M G , Takeshita Y , Madariaga J , Muenz L R , Hanna M G
Published: February 2017

PURPOSE

Patients with colon or rectal cancer were entered onto a prospectively randomized, controlled clinical trial of active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guérin (BCG) vaccine. We investigated whether ASI could improve disease-free status and survival.

PATIENTS AND METHODS

Ninety-eight patients with Dukes' stage B2-C3 colon or rectal cancer were randomized into groups treated by resection alone or resection plus ASI. Eighty patients met all eligibility criteria. All patients with rectal cancer were to receive 50 Gy of pelvic irradiation. Analysis of distribution of survival and disease-free survival was made on all eligible patients until December 31, 1990.

RESULTS

As a single study, no statistically significant differences were detected in survival or disease-free survival for all 80 eligible patients. However, since it was recognized at the outset that there were treatment differences, in that rectal cancer patients were to receive postimmunotherapy radiation, it was considered that a cohort analysis of the colon and rectal cancer patients might be informative. With a median follow-up of 93 months, there is a significant improvement in survival (two-sided P = .02; hazards ratio, 3.97) and disease-free survival (two-sided P = .039; hazards ratio, 2.67) in all eligible colon cancer patients who received ASI. With a median follow-up of 58 months, no benefits were seen in patients with rectal cancer who received ASI.

CONCLUSION

This study suggests that ASI may be beneficial to patients with colon cancer.
High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.
Authors: Crump M , Smith A M , Brandwein J , Couture F , Sherret H , Sutton D M , Scott J G , McCrae J , Murray C , Pantalony D
Published: February 2017

PURPOSE

To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS).

PATIENTS AND METHODS

Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm).

RESULTS

Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor.

CONCLUSION

Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.
Placebo-blinded study of morphine sulfate sustained-release tablets and immediate-release morphine sulfate solution in outpatients with chronic pain due to advanced cancer.
Authors: Finn J W , Walsh T D , MacDonald N , Bruera E , Krebs L U , Shepard K V
Published: February 2017

PURPOSE

This study was conducted to compare the relative analgesic efficacy and safety of an every-4-hour immediate-release oral morphine (IRM) solution with that of an every-12-hour sustained-release oral morphine (SRM) formulation.

PATIENTS AND METHODS

This was a double-blind, placebo-blinded, crossover study in 34 adult male and female outpatients with pain due to advanced cancer. Baseline data were collected on day 1. On days 2 and 3, randomly assigned patients received either placebo plus IRM (Roxanol; Roxane Laboratories, Inc, Columbus, OH; 20 mg/mL) at 2, 6, and 10 am, and 2, 6, and 10 pm, or alternatively SRM (Oramorph SR; Roxane Laboratories, Inc; 30 mg) at 10 AM and 10 PM. Patients were then crossed over to the alternate treatment for days 4 through 6. Pain relief was measured using a conventional 100-mm visual analog scale (VAS) and by recording the incidence of breakthrough pain. Information on side effects was obtained from VAS scores for sedation, nausea, anxiety, and depression; by directly questioning the patient as to mental confusion, bowel movements, and laxative use; and from Karnofsky performance status scores. VAS data were analyzed using a linear statistical model. Breakthrough pain data were analyzed using analysis of variance (ANOVA).

RESULTS

There were no statistically significant differences between IRM and SRM treatments with respect to VAS pain scores, side effect scores, or incidence of breakthrough pain data. Karnofsky performance scores remained stable for all patients throughout the study.

CONCLUSION

It was concluded that every-12-hour administration of SRM and every-4-hour administration of IRM provide similar analgesic effectiveness and side effect profiles in the treatment of chronic pain in cancer patients.
Parameters affecting the development of non-Hodgkin's lymphoma in patients with severe human immunodeficiency virus infection receiving antiretroviral therapy.
Authors: Pluda J M , Venzon D J , Tosato G , Lietzau J , Wyvill K , Nelson D L , Jaffe E S , Karp J E , Broder S , Yarchoan R
Published: February 2017

PURPOSE

To investigate the occurrence of non-Hodgkin's lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy and factors associated with the development of these lymphomas.

PATIENTS AND METHODS

The charts of 55 patients with advanced HIV infection receiving zidovudine (formerly known as azidothymidine [AZT])-based therapy and 61 patients receiving dideoxyinosine (ddI) were examined for the occurrence of NHL. Stored samples from the AZT-based treatment cohort were examined retrospectively for parameters predictive of the subsequent development of lymphoma.

RESULTS

Eight of 55 patients receiving AZT-based therapy developed NHL, yielding an estimated probability of 12% (95% confidence interval [CI], 4.7% to 27.1%) after 24 months, and 29.2% (95% CI, 15.2% to 48.7%) after 36 months. Four of 61 patients receiving ddI developed NHL, yielding a 6.2% (95% CI, 2.1% to 17%) estimated probability after 24 months, and 9.5% (95% CI, 3.6% to 22.8%) after 36 months. The difference between these cohorts was not significant (two-tailed P [P2] = .13). Patients with less than 50 CD4 cells/microL developed NHL at a significantly higher rate (P2 = .0085). This was particularly true for patients who presented with primary CNS lymphoma (PCNSL). For patients receiving AZT-based therapy, pretreatment serum interleukin-6 (IL-6) levels were somewhat higher in those who subsequently developed NHL than in those who did not (P2 = .048).

CONCLUSION

HIV-infected patients with profound immunodeficiency, especially those with less than 50 CD4 cells/microL, are at substantial risk of developing NHL and particularly PCNSL. Additional studies are needed to define the role of other factors such as IL-6 in the pathogenesis of these opportunistic tumors.
High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer.
Authors: Peters W P , Ross M , Vredenburgh J J , Meisenberg B , Marks L B , Winer E , Kurtzberg J , Bast R C , Jones R , Shpall E
Published: February 2017

PURPOSE

We studied high-dose cyclophosphamide, cisplatin, and carmustine (CPA/cDDP/BCNU) with autologous bone marrow support (ABMS) as consolidation after standard-dose adjuvant chemotherapy treatment of primary breast cancer involving 10 or more axillary lymph nodes.

PATIENTS AND METHODS

One hundred two women with stage IIA, IIB, IIIA, or IIIB breast cancer involving 10 or more lymph nodes at surgery were registered; 85 were eligible, treated, and assessable. Patients were treated with four cycles of standard-dose cyclophosphamide, doxorubicin, and fluorouracil (CAF), followed by high-dose CPA/cDDP/BCNU with ABMS.

RESULTS

Actuarial event-free survival for the study patients at a median follow-up of 2.5 years is 72% (95% confidence interval, 56% to 82%). Comparison to three historical or concurrent Cancer and Leukemia Group B (CALGB) adjuvant chemotherapy trials selected for similar patients showed event-free survival at 2.5 years to be between 38% and 52%. Therapy-related mortality was 12%; pulmonary toxicity of variable severity occurred in 31% of patients. Quality-of-life evaluations indicate that patients are functioning well without major impairments.

CONCLUSION

High-dose consolidation with CPA/cDDP/BCNU and ABMS after standard-dose CAF results in a decreased frequency of relapse in patients with high-risk primary breast cancer compared with historical series at the median follow-up of 2.5 years. Evaluation in a prospective, randomized trial is warranted and currently underway.
Dose-response relationship of epirubicin-based first-line chemotherapy for advanced breast cancer: a prospective randomized trial.
Authors: Focan C , Andrien J M , Closon M T , Dicato M , Driesschaert P , Focan-Henrard D , Lemaire M , Lobelle J P , Longree L , Ries F
Published: February 2017

PURPOSE

We compared prospectively the antitumor efficacy of two combination chemotherapy regimens with two different dose levels of epirubicin as first-line treatment for advanced breast cancer.

PATIENTS AND METHODS

One hundred forty-one fully assessable patients were randomized to receive either our intensified schedule (group A, n = 71) of epirubicin 50 mg/m2 on days 1 and 8 (every 3 weeks), or a non-intensified program (group B, n = 70) in which epirubicin was only administered on day 1. Both groups also received fluorouracil (5 FU) and cyclophosphamide 500 mg/m2 on day 1 of each course.

RESULTS

A statistically significant difference in response rate was observed (69% in group A v 41% in group B, P < .001) for both locally advanced (LA) and recurrent metastatic (RM) disease. Response duration (22 v 14 months, P < .01) and time to progression (TTP; 19 v 8 months, P < .02) were also significantly improved. Overall survival was similar in both groups. However, univariate and/or multivariate analyses showed a meaningful relationship between type of treatment allocated, dose-intensity (DI) of epirubicin, and response rate, as well as between TTP and survival. Ultimately, TTP and survival were also influenced by further treatment modalities, namely, hormonotherapy and chemotherapy.

CONCLUSION

This study validates prospectively the concept of a dose-response relationship for an anthracycline-based chemotherapy in previously untreated advanced breast cancer.
Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.
Authors: Thompson D S , Hainsworth J D , Hande K R , Holzmer M C , Greco F A
Published: February 2017

PURPOSE

This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms.

PATIENTS AND METHODS

Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion.

RESULTS

Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL.

CONCLUSION

Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.
Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam.
Authors: Razavi D , Delvaux N , Farvacques C , De Brier F , Van Heer C , Kaufman L , Derde M P , Beauduin M , Piccart M
Published: February 2017

PURPOSE AND METHODS

Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy (CT) has been reported, little has been done to develop strategies to prevent these problems. A double-blind, placebo-controlled study was therefore designed to assess the usefulness of adding low-dose alprazolam (0.5 mg to 2 mg per day) to a psychologic support program including progressive relaxation training designed to prevent the aforementioned conditions. Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment, which was conducted at four time points: before starting CT, 6 weeks after CT, before the fourth CT, and after the fourth CT. The Hospital Anxiety and Depression Scale (HADS), Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAS), Revised Symptom Checklist (SCL-90-R), Morrow Assessment of Nausea and Emesis (MANE), and World Health Organization (WHO) grading of acute and subacute toxicities were used to compare the alprazolam (AA) and placebo (PA) arms of the study.

RESULTS

At the second evaluation, the results showed a higher rate of anticipatory nausea (18% v 0%) in the PA compared with the AA arm (P = .038). These differences were no more significant at each of the further assessments. Significant differences were found for the intake of hypnotics at each assessment visit, with the rate of hypnotic users being significantly higher in the PA (19%) compared with the AA (0%) arm at the fourth assessment (P < .05). Anxiety and depression scores of self- and observer-report were similar in the two arms. A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline. The average HADS total score at baseline was 15.33 (SD = 6.56) for patients who developed anticipatory nausea and 11.23 (SD = 6.67) for other patients.

CONCLUSION

The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT. Although studies are needed to improve the efficacy reported here, physicians may already consider the use of alprazolam for cancer patients undergoing CT.
Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: a Childrens Cancer Group pilot study.
Authors: Woods W G , Kobrinsky N , Buckley J , Neudorf S , Sanders J , Miller L , Barnard D , Benjamin D , DeSwarte J , Kalousek D
Published: February 2017

PURPOSE

Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively timed induction therapy followed by autologous or allogeneic bone marrow transplantation (BMT) as the sole postremission therapy for newly diagnosed children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

PATIENTS AND METHODS

Between April 1988 and October 1989, 142 patients were eligible for study. All patients entered received a timing-intensive five-drug induction of dexamethasone, cytarabine (Ara-C), thioguanine, etoposide, and daunorubicin (DCTER) over 4 days with a second cycle administered after 6 days of rest, irrespective of hematologic status at that time. Most patients subsequently received a second two-cycle induction course. Those who achieved remission were eligible for bone marrow ablative therapy with busulfan and cyclophosphamide, followed by 4-hydroperoxy-cyclophosphamide (4-HC)-purged autologous or allogeneic BMT rescue.

RESULTS

One hundred eight (76%) patients achieved remission: 19 (13%) died of complications of the leukemia and/or chemotherapy, and 15 (11%) failed to achieve remission. Seventy-four patients subsequently underwent BMT with either autologous (n = 58) or allogeneic (n = 16) rescue. For patients who received autologous rescue with 4-HC-purged grafts, the actuarial disease-free survival (DFS) rate at 3 years from the day of transplant is 51%, compared with 55% for patients who received allogeneic grafts (P = .92). At 3 years, the overall actuarial survival rate for all 142 patients entered on this study is 45%, with an event-free survival (EFS) rate of 37%. Adverse prognostic factors for outcome included an elevated WBC count or the presence of CNS leukemia at the time of AML diagnosis.

CONCLUSION

Results suggest that aggressively timed induction therapy followed by marrow ablation and BMT rescue with either autologous or allogeneic grafts for children with newly diagnosed AML or MDS is both feasible and effective.
High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas.
Authors: Heideman R L , Douglass E C , Krance R A , Fontanesi J , Langston J A , Sanford R A , Kovnar E H , Ochs J , Kuttesch J , Jenkins J J
Published: February 2017

PURPOSE

Evaluation of high-dose chemotherapy with autologous bone marrow rescue (ABMR) in pediatric malignant gliomas.

PATIENTS AND METHODS

Newly diagnosed (n = 11) and recurrent (n = 2) malignant glioma patients received high-dose chemotherapy within 4 weeks of surgery; three had near total and 10 had subtotal resection/biopsy. High-dose thiotepa (300 mg/m2) and cyclophosphamide (2 g/m2) daily for 3 days were followed by ABMR; response was evaluated at day 30. At day 60, patients with at least stable disease received hyperfractionated (n = 9) or conventional external-beam radiotherapy (n = 2) preceded by local radioactive iodine 125 implantation (n = 2) or radiosurgery (n = 1).

RESULTS

Grade III and IV toxicities after ABMR consisted of mucositis (n = 12), cardiomyopathy (n = 1), acute abdomen (n = 1), pneumonitis (n = 2), and infection (n = 2). One complete and three partial responses were observed; the objective response rate was 31% (95% confidence interval, 9% to 61%). Seven had stable disease, one had disease progression, and one died of toxicity before response evaluation. The median overall and progression-free survival durations after combined modality therapy were 14 months (range, 4 to 30+) and 9 months (range, 0 to 30+), respectively. One patient remains progression-free at 30+ months. Radionecrosis and white matter changes occurred in three patients: one after hyperfractionated irradiation, and two after 125I implants.

CONCLUSION

For patients with bulky residual disease after surgery, survival with this aggressive chemotherapy and radiation regimen is not better than that reported for conventional treatment regimens.
Persistence of circulating t(14;18)-positive cells in long-term remission after radiation therapy for localized-stage follicular lymphoma.
Authors: Finke J , Slanina J , Lange W , Dölken G
Published: February 2017

PURPOSE

To determine the prevalence of circulating t(14;18)-positive cells in patients with long-term remission after radiation therapy for stage I and II follicular lymphoma.

PATIENTS AND METHODS

Peripheral-blood mononuclear cells from 21 patients in continuous remission were examined by a two-step polymerase chain reaction (PCR) assay for the detection of cells carrying a t(14;18) translocation with a breakpoint within the major breakpoint region (MBR) or minor cluster region (mcr).

RESULTS

Follow-up duration was between 25 and 160 months, with a median of 6.5 years. Thirteen patients (62%) showed negative results on repetitive testing. Cells that were t(14;18)-positive were found in eight patients (38%), all carrying a breakpoint in the MBR. One patient relapsed in each group.

CONCLUSION

Circulating t(14;18)-positive cells can persist in a high percentage of follicular lymphoma patients in long-term complete remission (CR) after radiation treatment for stage I and II disease. The significance of minimal residual t(14;18)-positive cells with regard to the risk of relapse needs to be investigated in further prospective long-term studies.
Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma.
Authors: Grem J L , Jordan E , Robson M E , Binder R A , Hamilton J M , Steinberg S M , Arbuck S G , Beveridge R A , Kales A N , Miller J A
Published: February 2017

PURPOSE

To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study.

PATIENTS AND METHODS

Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity.

RESULTS

Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity.

CONCLUSION

This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.
Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.
Authors: Rivkin S E , Green S , Metch B , Cruz A B , Abeloff M D , Jewell W R , Costanzi J J , Farrar W B , Minton J P , Osborne C K
Published: February 2017

PURPOSE

To compare chemohormonal therapy, chemotherapy alone, and hormonal therapy alone in postmenopausal patients with estrogen receptor (ER)-positive operable breast cancer and positive axillary nodes with respect to survival and disease-free survival (DFS).

PATIENTS AND METHODS

Eight hundred ninety-two postmenopausal women with ER-positive, node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) from July 1979 to March 1989 and 74 by the Eastern Cooperative Oncology Group (ECOG) between June 1987 and March 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive the following: (1) tamoxifen 10 mg twice daily by mouth for 1 year; (2) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (IV) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 IV weekly for 1 year, vincristine .625 mg/m2 IV weekly for the first 10 weeks, and prednisone during weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (3) the combination of tamoxifen and CMFVP.

RESULTS

The median follow-up duration is 6.5 years, with a maximum of 12.8 years. Treatment arms are not significantly different with respect to either survival or DFS (log-rank, 2 df, P = .82 and .23, respectively). The 5-year survival rate is 77% for the tamoxifen arm, 78% for CMFVP, and 75% for the combination. No significant differences were observed in node or receptor level subsets. Severe or worse toxicity was experienced by 56% of patients on CMFVP and 61% on CMFVP plus tamoxifen, compared with 5% on tamoxifen alone.

CONCLUSION

CMFVP chemotherapy, either alone or in combination with tamoxifen, has not been shown to be superior to tamoxifen alone in the treatment of postmenopausal women with node-positive, ER-positive, operable breast cancer.
Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer.
Authors: Toussaint C , Izzo J , Spielmann M , Merle S , May-Levin F , Armand J P , Lacombe D , Tursz T , Sunderland M , Chabot G G
Published: February 2017

PURPOSE

A phase I/II trial of vinorelbine (VRL) administered by continuous infusion (CIV) was conducted in advanced breast carcinoma (ABC) patients to determine the maximum-tolerated dose (MTD) and to evaluate the toxicity pattern and antitumor activity of this alternative administration schedule to the currently recommended weekly short intravenous (IV) administration.

PATIENTS AND METHODS

Between February 1990 and July 1991, 64 consecutive, eligible patients with ABC were treated; 33 had received one or two previous palliative chemotherapy combinations and 31 had not received chemotherapy for metastatic disease. VRL was administered, after an initial IV bolus of 8 mg/m2 on day 1, by a 4-day CIV at five different 24-hour dose levels (DLs) to be repeated every 21 or 28 days: DL1, 5.5 mg/m2; DL2, 7 mg/m2; DL3, 8 mg/m2, DL4, 9 mg/m2; and DL5, 10 mg/m2.

RESULTS

The limiting noncumulative toxicity was neutropenia, with the MTD established at 8 mg/m2 bolus plus 10 mg/m2/d for 4 days (total dose per cycle, 48 mg/m2). At DL3 and DL4, we observed mucositis (14% of patients; five percent of cycles > grade 2), alopecia, and asthenia. By contrast, neurotoxicity was minor. The toxicity was otherwise predictable and manageable. Pharmacokinetic data obtained at DL1 and DL3 showed a mean VRL plasma concentration of 967 +/- 331 ng/mL after the initial 8 mg/m2 IV bolus dose, which declined rapidly thereafter to reach mean steady-state levels of 12 ng/mL (n = 5) for the 30-mg/m2 dose and 8 ng/mL (n = 2) for the 40-mg/m2 dose. These levels were maintained over the 96-hour CIV. The mean residence time (MRT) was 29 +/- 7 hours (terminal half-life [t1/2], 23 hours), the total-body clearance (CL) was 24 +/- 11 L/hr/m2, and the volume of distribution at steady-state (Vss) was high at 1,832 +/- 359 L/m2. Two patients achieved a complete response (CR) and 21 a partial response (PR), for an objective response rate of 36% (95% confidence interval [Cl], 23 to 49). The median duration of response was 6 months. The median survival duration was 24 months (range, 3 to 37). A relationship between given dose-intensity and objective response rate was found, with an overall response (OR) rate of 13.3% (two of 15) for 8 to 10 mg/m2/wk, 35.4% (11 of 31) for 10 to 12 mg/m2/wk, and 55.5% (10 of 18) for 12 to 14.5 mg/m2/wk.

CONCLUSION

This trial, while confirming VRL activity in ABC, shows the feasability of a CIV administration schedule. A decrease of the administrated total dose per 3- to 4-week cycle to less than the weekly schedule with the same therapeutic activity suggests a better therapeutic index. The data are also suggestive of a dose-response relationship and a dose-intensity/activity correlation.
Multiple atypical nevi: a cutaneous marker of germ cell tumors.
Authors: Raghavan D , Zalcberg J R , Grygiel J J , Teriana N , Cox K M , McCarthy W , Flynn M
Published: February 2017

PURPOSE

This study assessed whether a specific association exists between atypical nevi and germ cell tumors (GCT).

METHODS

A prospective comparison was performed on a cohort of 129 unselected patients with GCT and a series of 153 healthy men. Three or more of the following criteria were required for diagnosis of multiple atypical nevi: greater than 5 mm in diameter; variegated color, often speckled black/brown, with irregularly distributed pigmentation; irregular outline or indistinct border; and at least three such lesions.

RESULTS

Prevalences for multiple atypical nevi in patients with GCT and in healthy controls were 37% and 15%, respectively (P < .01). Two patients with these lesions also had documented malignant melanoma. In contrast, 16% of patients with GCT had a history of testicular maldescent (the most common known risk factor), compared with 5% of healthy controls (P < .01).

CONCLUSION

Multiple atypical nevi occur with a statistically significant increased prevalence in patients with GCT as compared with healthy controls, and constitute one of the most common known clinical associations with this malignancy. These data may be of relevance for our understanding of the biology of GCT and of malignant melanoma, in the design of screening programs for testis cancer, and in the follow-up evaluation of patients with each of these disorders.
Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer.
Authors: Scambia G , Benedetti Panici P , Foti E , Amoroso M , Salerno G , Ferrandina G , Battaglia F , Greggi S , De Gaetano A , Puglia G
Published: February 2017

PURPOSE

The aim of the study was to investigate the role of squamous cell carcinoma antigen (SCC) in the management of patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery.

PATIENTS AND METHODS

SCC assay was performed with a radioimmunoassay kit in a series of 102 patients with locally advanced cervical cancer. The values of 2.5, 5, and 7 ng/mL were used to define SCC antigen positivity. The chi 2 and Fisher's exact test and the stepwise logistic regression were used to evaluate the distribution of marker values. Analysis of survival was performed using the Kaplan and Meier test and Cox multivariate regression analysis.

RESULTS

SCC levels were elevated in 65%, 45%, and 32% of patients with primary tumors for cutoff values of 2.5, 5, and 7 ng/mL, respectively. SCC pretreatment levels correlated with stage, tumor volume and lymph node status. In the multivariate analysis, SCC expression proved to be an independent predictor of response to neoadjuvant chemotherapy. SCC posttreatment levels were strongly related to chemotherapy response. Moreover, the overall correlation between the clinical course of the disease and the variation of SCC levels was 83%. In patients with squamous cell tumors, survival was significantly longer in SCC-negative cases compared with SCC-positive cases (P = .04). Moreover, in patients undergoing surgery after response to neoadjuvant chemotherapy, low SCC values were associated with better prognosis (P = .02). In the multivariate analysis, parametrial involvement and SCC status proved to retain an independent prognostic value.

CONCLUSION

Our data show that SCC assay may provide useful information to improve the prognostic characterization and disease monitoring of patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.
Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer.
Authors: Jett J R , Maksymiuk A W , Su J Q , Mailliard J A , Krook J E , Tschetter L K , Kardinal C G , Twito D I , Levitt R , Gerstner J B
Published: February 2017

PURPOSE

We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR).

PATIENTS AND METHODS

One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months.

RESULTS

Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years.

CONCLUSION

Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.
Altered etoposide pharmacokinetics and time to engraftment in pediatric patients undergoing autologous bone marrow transplantation.
Authors: Rodman J H , Murry D J , Madden T , Santana V M
Published: February 2017

PURPOSE

To determine the pharmacokinetics and clinical response of high-dose etoposide in combination with carboplatin for pediatric cancer patients undergoing autologous bone marrow transplant.

PATIENTS AND METHODS

Pharmacokinetic parameters for etoposide were determined at doses of 960, 1,200, and 1,500 mg/m2 when given with high-dose carboplatin and followed by autologous marrow rescue. Twenty-nine patients (age 1.6 to 23 years) with refractory or relapsed solid tumors were studied. Etoposide was administered in three divided doses as a 6-hour infusion on alternate days with carboplatin. Etoposide concentrations (n = 14) were determined during and following each of three doses. Patient characteristics, drug dose, and pharmacokinetic parameters were examined as predictors of marrow engraftment as reflected by recovery of granulocytes and platelets.

RESULTS

The median values for clearance (Cl) and terminal half-life (T1/2 beta) of etoposide were 14.3 mL/min/m2 (range, 6.8 to 29.6) and 5.9 hours (range, 3.7 to 39). After adjustment for body size, Cl and volume of distribution did not correlate with any laboratory parameter or patient characteristic. However, seven patients who received concomitant anticonvulsant therapy had significantly higher (P < .01) average etoposide Cl values (23.7 mL/min/m2) than 22 patients who did not receive drugs known to alter hepatic metabolism (13.4 mL/min/m2). The median etoposide Cl value in patients who received concurrent carboplatin but no anticonvulsant agents is substantially lower than values previously reported in either children or adults. Higher etoposide concentrations were significantly associated with longer times to recovery of granulocyte and platelet counts.

CONCLUSION

Etoposide Cl is significantly higher in patients who receive concomitant anticonvulsant therapy, which is consistent with clinically important hepatic enzyme induction. The lower etoposide Cl associated with high-dose carboplatin suggests that carboplatin may impair etoposide metabolism. Furthermore, high etoposide concentrations appeared to prolong time to recovery of hematopoietic function.
Multidrug resistance in lymphomas.
Authors: Yuen A R , Sikic B I
Published: February 2017

PURPOSE

To discuss the significance of multidrug resistance (MDR) in human lymphomas and to review recent and ongoing clinical trials using MDR modulators.

DESIGN

A medical literature search was used to identify articles that reported results on the expression or modulation of MDR in human lymphomas. This review summarizes the various methods for detecting expression of the mdr1 gene in tumor specimens, the patterns of expression in lymphomas, and recent and upcoming clinical trials using modulating agents to reverse MDR.

RESULTS

There is considerable variation in the assays used to evaluate the expression of mdr1 in lymphomas. Current methodology includes reverse transcriptase polymerase chain reaction (rt-PCR) for assay of mdr1 mRNA, and immunohistochemistry or flow cytometry for detection of the multidrug transporter, P-glycoprotein (P-gp). The preponderance of evidence suggests that mdr1 expression is relatively low in untreated patients (10% to 20% of lymphomas positive), but increases in patients with recurrent disease (50% to 70% positive). Some evidence suggests that mdr1 expression is a prognostic factor for response to chemotherapy, as well as for subsequent survival. Verapamil and cyclosporine (CsA) have been used as competitive inhibitors of the multidrug transporter P-gp in early clinical trials. Although these studies show some activity in modulating clinical MDR, both verapamil and CsA manifest considerable toxicities at doses below those required for complete inhibition of P-gp function.

CONCLUSION

MDR due to the expression of the mdr1 gene is an important factor in the course of patients with lymphomas. Continued clinical trials with more potent and less toxic modulators are needed to define the ultimate benefit of modulating MDR in lymphomas.
Low numbers of CSF blasts at diagnosis do not predict for the development of CNS leukemia in children with intermediate-risk acute lymphoblastic leukemia: a Childrens Cancer Group report.
Authors: Gilchrist G S , Tubergen D G , Sather H N , Coccia P F , O'Brien R T , Waskerwitz M J , Hammond G D
Published: February 2017

PURPOSE

This study was designed to evaluate the effect on CNS relapse (CNSR) and overall relapse rates of blast cells in the CSF containing < or = 5 cells/microL at the time of diagnosis of intermediate-risk acute lymphoblastic leukemia (ALL) in children entered onto a large randomized multicenter prospective therapeutic trial (Childrens Cancer Group [CCG]-105).

PATIENTS AND METHODS

We studied outcome in terms of CNSR and event-free survival (EFS) in 1,544 patients who successfully completed remission-induction therapy and had been randomized to one of four systemic chemotherapy regimens and to one of two CNS prophylaxis regimens. We compared outcome between 1,450 patients who had varying degrees of pleocytosis but no blasts in the CSF at diagnosis (blast-negative group) with 94 who had blasts detected in the CSF after cytocentrifugation but had a total CSF WBC count of < or = 5/microL (blast-positive group).

RESULTS

No statistically significant differences in overall CNSR or EFS rates were observed between the two groups and no differences were found when analyzed according to age or WBC count at diagnosis, sex, or type of CNS prophylaxis (intrathecal [IT] methotrexate [MTX] alone v IT MTX plus 18 Gy cranial irradiation [CXRT]).

CONCLUSION

In intermediate-risk ALL, there was no significant difference in CNSR and systemic relapse rates after standard presymptomatic CNS therapy between patients with a CSF WBC count < or = 5/microL and those without identifiable blasts in the CSF. These findings suggest that certain approaches to therapy, such as that used in this study, may eliminate the need for any additional special treatment directed at this subset of patients with CSF blasts.