bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter phase II efficacy trial of toremifene in tamoxifen-refractory patients with advanced breast cancer.
Authors: Vogel C L , Shemano I , Schoenfelder J , Gams R A , Green M R
Published: February 2017

PURPOSE

To explore further the efficacy of high-dose toremifene in patients with advanced breast cancer who had failed to respond to tamoxifen or whose disease had progressed on tamoxifen.

PATIENTS AND METHODS

One hundred two perimenopausal or postmenopausal women with metastatic breast cancer refractory to tamoxifen were entered onto a phase II clinical trial of toremifene at a dose of 200 mg/d. The study patients consisted of 28 primarily refractory patients; 43 patients who had relapsed after a prior tamoxifen response; and 31 patients who had relapsed while receiving adjuvant tamoxifen. This was a heavily pretreated group of patients, with 65% having failed chemotherapeutic attempts and 72% having failed two or more hormonal therapies. Forty-nine percent of patients had visceral dominant disease.

RESULTS

The objective response rate was 5% (95% confidence interval [CI], 3% to 7%). The median time to treatment failure (TTF) was 10.9 months for the five responders. An additional 23% of patients had stable disease for a median TTF of 7.8 months, whereas the patients who experienced treatment failure had a median TTF of 2.1 months. Whether those patients with stable disease derived clinical benefit or simply had slow progression in an intrinsically indolent disease presentation is uncertain. Common toxicities were generally mild and similar to those encountered with tamoxifen.

CONCLUSION

We conclude that there is major cross-resistance between tamoxifen and toremifene and that only occasional tamoxifen-refractory patients will have objective responses to toremifene.
Multiple brain metastases are associated with poor survival in patients treated with surgery and radiotherapy.
Authors: Hazuka M B , Burleson W D , Stroud D N , Leonard C E , Lillehei K O , Kinzie J J
Published: February 2017

PURPOSE

A retrospective analysis was performed to evaluate the role of surgery in the management of patients with solitary and multiple brain metastases.

PATIENTS AND METHODS

Between 1980 and 1990, 46 patients underwent surgical resection of brain metastases at the University of Colorado Health Sciences Center. All but two patients received postoperative whole-brain radiotherapy to a median total dose of 30 Gy (range, 11.4 Gy to 50.0 Gy). Lung was the most common (56%) primary site and adenocarcinoma was the most common (46%) tumor histology. Twenty-eight of 46 patients (61%) had solitary metastases, while the remaining 18 patients had two or more foci.

RESULTS

The median survival of all 46 patients was 11 months, and the 1- and 2-year survival rates were 40% and 12%, respectively. Moderately severe to severe neurologic impairment at the time of diagnosis and the presence of multiple brain metastases were associated with a significantly poorer survival. In patients with solitary metastasis, gross total resection and adenocarcinoma tumor histology significantly prolonged survival, whereas primary tumor site, the presence of active extracranial disease, and radiation dose had no significant effect on survival.

CONCLUSION

These results are consistent with a recent randomized study supporting the role of surgery and whole-brain radiation therapy in the management of patients with solitary brain metastases. We would caution against the generalization of this concept to patients with two or more brain metastases.
Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration.
Authors: Blomqvist C , Elomaa I , Rissanen P , Hietanen P , Nevasaari K , Helle L
Published: February 2017

PURPOSE

To compare the effect on toxicity and efficacy of the fluorouracil 500 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) regimen divided into 4 weekly doses with conventional every-4-week administration in metastatic breast cancer.

PATIENTS AND METHODS

The inclusion criteria demanded measurable or assessable metastases from breast cancer and a World Health Organization (WHO) performance index of 2 or less. One hundred seventy-three patients with metastatic breast cancer who had not been treated with anthracyclines were randomized to receive FEC once every 4 weeks or once a week. The scheduled monthly doses of the cytotoxic agents were identical in both groups. Three patients were excluded from analysis.

RESULTS

Hematologic toxicity, alopecia, nausea, and vomiting were significantly more severe in the group that received treatment every 4 weeks. The response rate was higher in the group that received FEC every 4 weeks than in the group treated weekly (47% v 30%, P = .02). Time to progression was significantly (P = .005) longer with every-4-week FEC treatment (median, 9.2 months v 5.4 months for weekly treatment). Patients in the group treated every 4 weeks lived significantly (P = .01) longer than patients treated weekly (median survival times, 21.2 months v 11.8 months, respectively). The actually delivered monthly dose levels and treatment duration were similar in the two groups.

CONCLUSION

Both efficacy and toxicity of FEC were greater when treatment was administered every 4 weeks rather than once a week, despite identical dose intensity.
High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients.
Authors: Magriples U , Naftolin F , Schwartz P E , Carcangiu M L
Published: February 2017

PURPOSE

Several reports have associated tamoxifen administration with endometrial carcinoma. A retrospective study of the histologic features of uterine cancer in patients with a history of breast carcinoma was undertaken to determine the effect of treatment with tamoxifen.

MATERIALS AND METHODS

A computer search of the Yale-New Haven Hospital Tumor Registry from 1980 to 1990 identified 53 patients with a history of breast carcinoma who subsequently developed a malignant tumor of the uterine corpus.

RESULTS

Fifteen patients received tamoxifen for breast carcinoma and 38 did not. The mean ages of the two groups were not significantly different. The mean interval between detection of breast and endometrial cancers was 5 years in the tamoxifen group and 12 years in the nontreated group (P = .0023). Sixty-seven percent of patients in the tamoxifen group had poorly differentiated endometrioid carcinomas (including adenosquamous carcinoma) or carcinomas associated with poor outcome (eg, uterine papillary serous carcinoma, clear-cell carcinoma, or mixed müllerian tumor), as compared with 24% in the nontreated group (P = .03). Patients in the tamoxifen group were much more likely to die of endometrial cancer (33.3% v 2.6% of the nontreated group, P = .005).

CONCLUSION

From this retrospective study, it appears that women receiving tamoxifen as treatment for breast cancer who subsequently develop uterine cancer are at risk for high-grade endometrial cancers that have a poor prognosis. These findings also indicate that tamoxifen-associated uterine cancers may have a different basis from those associated with steroidal estrogen treatment.
Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial.
Authors: Tubergen D G , Gilchrist G S , O'Brien R T , Coccia P F , Sather H N , Waskerwitz M J , Hammond G D
Published: February 2017

PURPOSE

The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program.

PATIENTS AND METHODS

Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs.

RESULTS

The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT.

CONCLUSION

Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age.
Impact of high-dose cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report from the Childrens Cancer Group.
Authors: Wells R J , Woods W G , Lampkin B C , Nesbit M E , Lee J W , Buckley J D , Versteeg C , Hammond G D
Published: February 2017

PURPOSE

The purpose of this review was to determine the impact of high-dose cytarabine and asparaginase intensification, administered shortly after remission induction, on the outcome of childhood acute myeloid leukemia (AML).

MATERIALS AND METHODS

Three consecutive Childrens Cancer Group (CCG) trials of acute myeloid leukemia, CCG 251 (1979 to 1983), CCG 213P (1983 to 1985), and CCG 213 (1985 to 1989) with a total of 1,294 patients, were reviewed and provide the basis of this report.

RESULTS

CCG 213P demonstrated the importance of dose interval, in that two courses of cytarabine and asparaginase administered at 7-day intervals gave superior 5-year survival rates (58% v 41% from the end of induction, P < .04) to the same therapy administered at 28-day intervals. CCG 213 showed that there was no advantage to the maintenance therapy used for patients who received two courses of cytarabine and asparaginase at 7-day intervals (5-year survival, 68% [no maintenance] v 44% [maintenance] from the end of consolidation, P < .01). Inclusion of the 7-day interval cytarabine/asparaginase intensification was accompanied by an overall improvement in 5-year survival rates from diagnosis when compared with historical controls (CCG 213, 36% v CCG 251, 29%, P < .02) although other differences between these studies could also be responsible for the improvement seen.

CONCLUSION

High-dose cytarabine and asparaginase intensification eliminated the benefit of prolonged maintenance therapy in childhood AML and was accompanied by an overall improvement in survival.
Prognostic factors in medulloblastoma, including DNA ploidy.
Authors: Zerbini C , Gelber R D , Weinberg D , Sallan S E , Barnes P , Kupsky W , Scott R M , Tarbell N J
Published: February 2017

PURPOSE

DNA ploidy status, completeness of surgical resection, use of chemotherapy, adequacy of radiation therapy, metastatic stage, sex, and age at diagnosis were evaluated as predictors of relapse in 58 patients with cerebellar medulloblastoma.

METHODS

Flow cytometry (FCM) and/or image analysis (IA) were used to characterize tumor DNA ploidy. Twelve tumors (21%) were found to be aneuploid, 11 (19%) tetraploid, and 35 (60%) diploid.

RESULTS

The most significant predictors of relapse in univariate analyses were the adequacy of radiation (> or = 50 Gy) (P = .02), metastatic staging (P = .05), completeness of resection (P = .085), and DNA ploidy status (diploid/tetraploid v aneuploid; P = .11). When the 52 patients who received > or = 50 Gy were included in a multivariate Cox model analysis, those with diploid/tetraploid tumors had fewer recurrences than those with aneuploid tumors (relative risk, 0.33; 95% confidence interval, 0.12 to 0.89; P = .03). Patients with complete resections (P = .07), or with stage M0 disease (P = .06) had fewer recurrences than other patients, but these factors were not independent predictors of outcome. DNA ploidy status was correlated with age; 10 of the 12 aneuploid tumors were found in children ages 3 to 10 years. Age, sex, and the use of chemotherapy were not prognostically significant in these analyses.

CONCLUSION

The adequacy of radiation dose and DNA ploidy were the most important prognostic factors in this series. Contrary to previous reports, when corrected for adequacy of treatment, DNA aneuploidy was associated with a poor outcome. By multivariate analyses, DNA ploidy was an independent variable, even when controlling for extent of surgical resection and metastatic stage.
Role of computed tomography in the staging of primary melanoma.
Authors: Buzaid A C , Sandler A B , Mani S , Curtis A M , Poo W J , Bolognia J L , Ariyan S
Published: February 2017

PURPOSE

To evaluate the role of body computed tomography (CT) for the staging of patients with early melanoma.

PATIENTS AND METHODS

A total of 151 new patients with American Joint Committee (AJC) clinical stage I, II, and III melanoma who received a CT scan of at least the chest and abdomen are the subject of this study. CT scans considered suspicious for metastases were reviewed again by one of the investigators (A.McB.C.).

RESULTS

Of 151 patients, 63 had AJC clinical stage I, 61 stage II, and 23 stage III disease. In addition, one patient each had primary melanoma of the anal canal, esophagus, or vulva. Twenty-nine (19%) of 151 patients had a CT scan that was considered suspicious for metastases. The most common radiologic findings were single hepatic, and single or multiple pulmonary nodules. Of these 29 patients with suspicious scans, 24 subsequently proved to have benign processes by biopsy or follow-up studies, three had second primary tumors (well-differentiated lymphocytic lymphoma, Hodgkin's disease, and renal cell carcinoma), and only two were found to have metastatic melanoma. Of these two patients, one had regional nodal disease (unsuspected on physical examination) and one had distant nodal metastases.

CONCLUSION

Body CT is not a useful imaging study in the detection of occult metastases in patients with primary melanoma. Although body CT commonly shows suspicious radiologic abnormalities in patients with early melanoma, these abnormalities most likely represent benign processes or a second primary tumor, rather than metastatic melanoma. The value of body CT in patients who present with nodal metastases needs further study.
Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia.
Authors: Tallman M S , Hakimian D , Shaw J M , Lissner G S , Russell E J , Variakojis D
Published: February 2017

PURPOSE

Since the only three cases of granulocytic sarcoma among patients with acute myeloid leukemia (AML) seen at our institution during the last 12 years were each associated with the 8;21 translocation [t(8;21)], we sought to determine if this association is specific and more frequent than previously recognized.

PATIENTS AND METHODS

We report three patients with AML and t(8;21) who developed granulocytic sarcomas, and review the world literature.

RESULTS

Between 1980 and 1992, 53 cases of AML French-American-British (FAB) M2 were identified at our institution. Eight (15%) patients had t(8;21). Three of these eight patients (38%) developed granulocytic sarcoma. All three of our patients received conventional intensive antileukemic chemotherapy yet had short relapse-free survival durations. Several series of patients with t(8;21) report that granulocytic sarcomas occur in approximately 18% of this population, which is four times the expected incidence in AML. Thirty-seven cases have been previously reported. Although karyotype analyses were not reported in many cases of granulocytic sarcoma in the literature, the vast majority of abnormal karyotypes in patients with AML involved t(8;21). Recent work with a cell line derived from a patient with t(8;21) indicates that such cells are unusually adherent to culture bottles and are aggregable

CONCLUSION

Our data suggest that this association is more common than generally recognized and may be specific. Patients with t(8;21) should be observed closely for signs and symptoms of granulocytic sarcoma. These patients may have a less favorable prognosis than other patients with t(8;21). Cooperative oncology groups should retrospectively identify patients with AML and t(8;21) who had a poor outcome to determine if they had a disproportionate incidence of granulocytic sarcoma. If so, aggressive therapy such as bone marrow transplantation may be warranted early in the therapeutic strategy.
Postchemotherapy rheumatism.
Authors: Loprinzi C L , Duffy J , Ingle J N
Published: February 2017

PURPOSE

This report describes a previously unreported clinical phenomenon that occurs in some patients after completion of combination chemotherapy.

METHODS AND RESULTS

Eight case reports are presented. Affected patients developed a syndrome of myalgias/arthralgias within several months of completing cyclophosphamide/fluorouracil (5FU)-containing adjuvant combination chemotherapy for breast cancer. These symptoms did not appear to be related to cancer recurrence or any common rheumatologic disorder. The syndrome generally resolved over several months.

CONCLUSION

Postchemotherapy rheumatism is a syndrome of myalgias/arthralgias that usually develops 1 to 3 months after completion of adjuvant chemotherapy. Recognition of this syndrome can limit the need for extensive work-ups to exclude recurrent breast cancer or inflammatory rheumatologic diseases.
Should the elderly receive chemotherapy for node-negative breast cancer? A cost-effectiveness analysis examining total and active life-expectancy outcomes.
Authors: Desch C E , Hillner B E , Smith T J , Retchin S M
Published: February 2017

PURPOSE

This study determines the survival benefit and cost-effectiveness of adjuvant chemotherapy in elderly women with breast cancer. In addition, the analysis measures the impact of substituting active life expectancy for survival in the clinical decision.

PATIENTS AND METHODS

Two cohorts of women with estrogen receptor (ER)-negative, stage I breast cancer from age 60 to 80 years were monitored using a Markov process. One group received standard chemotherapy following primary therapy, and the other had no postoperative treatment. Data were derived from recently published clinical trials and a major meta-analysis. Outcome included the average survival, active life-expectancy, and incremental cost/quality-adjusted life-year (cost/QALY).

RESULTS

Adjuvant chemotherapy prolongs survival in older women, but to a lesser extent compared with younger women. The average gain in quality-adjusted months was 1.8 months in a 75-year-old cohort at a cost/QALY of $4,400. These small benefits were not substantially altered when univariate changes were made in toxicity, recurrence risk, or effectiveness of chemotherapy. When active life expectancy replaced survival as an end point, the benefit for 75-year-old women decreased to 2 weeks at a cost of more than $96,000/QALY.

CONCLUSION

There is a small survival benefit for adjuvant chemotherapy in elderly patients. The cost of this benefit is high, but within the range of commonly reimbursed procedures until a point between 75 and 80 years old. The use of active life expectancy as the primary outcome reduces the benefit and adds to the cost. If physicians and policymakers agree that active life expectancy is a relevant outcome, withholding chemotherapy for patients > or = 70 years old is a reasonable approach.
Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group.
Authors: Gandara D R , Crowley J , Livingston R B , Perez E A , Taylor C W , Weiss G , Neefe J R , Hutchins L F , Roach R W , Grunberg S M
Published: February 2017

PURPOSE

To test the concept that cisplatin dose-intensity is important in the treatment of non-small-cell lung cancer (NSCLC), the Southwest Oncology Group (SWOG) performed a randomized trial comparing standard-dose cisplatin (SDCP) 50 mg/m2 days 1 and 8 on a 28-day cycle for eight cycles, high-dose cisplatin (HDCP) 100 mg/m2 days 1 and 8 for four cycles, and high-dose cisplatin plus mitomycin (HDCP-M) 8 mg/m2 day 1. To isolate the effects of dose-intensity versus total dose, the planned cumulative cisplatin dose was 800 mg/m2 in each arm.

PATIENTS AND METHODS

Between July 1988 and April 1990, 356 patients were enrolled and 323 were eligible and assessable. All patients had metastatic, measurable disease, were chemotherapy-naive, and had a performance status (PS) of 0 to 2.

RESULTS

Confirmed complete plus partial response rates were SDCP, 12%; HDCP, 14%; and HDCP-M, 27% (P < .05). Complete responses were uncommon (HDCP, 3%; HDCP-M, 4%) and were observed only in the high-dose arms. Progressive disease occurred more frequently in the SDCP arm (57%) compared with HDCP (38%) or HDCP-M (34%) (P < .05). However, there were no significant differences in median survival times (SDCP, 6.9 months; HDCP, 5.3 months; HDCP-M, 7.2 months; P = .53). The mean delivered dose-intensity for cisplatin was significantly greater in the high-dose arms: HDCP 41 mg/m2/wk and HDCP-M 39 mg/m2/wk, versus SDCP 23 mg/m2/wk (P = .05). The high-dose arms resulted in an increased incidence of ototoxicity, emesis, and myelosuppression, but similar degrees of renal toxicity and neuropathy compared with SDCP.

CONCLUSION

This study does not confirm evidence of a steep clinical dose-response curve for cisplatin in NSCLC at the cisplatin dose-intensities achieved. The addition of mitomycin increases the response rate, but does not improve survival. Continued evaluation of new agents in this disease is warranted.
Splenectomy and the increasing risk of secondary acute leukemia in Hodgkin's disease.
Authors: Tura S , Fiacchini M , Zinzani P L , Brusamolino E , Gobbi P G
Published: February 2017

PURPOSE

Following irradiation alone, secondary acute nonlymphocytic leukemia (ANLL) is uncommon; following chemotherapy alone, the risk is increased, but not as much as when combined modality treatments are used. Because ANLL seems more likely to occur in splenectomized patients, attention is focused on an unexpected association between splenectomy and the risk of secondary leukemia.

PATIENTS AND METHODS

The risk of ANLL was assessed in 503 patients with Hodgkin's disease (HD) homogeneously treated with combined modality therapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP] plus radiotherapy). These patients were diagnosed from 1970 through 1984 and monitored until June 1991.

RESULTS

ANLL was observed in one of 145 (0.69%) patients not splenectomized and in 21 of 358 (5.86%) splenectomized patients, demonstrating a significantly higher frequency of ANLL in the group of patients who underwent splenectomy. The group of patients who developed ANLL received a statistically greater number of MOPP courses than did the group not developing ANLL. ANLL was statistically more frequent in those patients who received more than four cycles of MOPP. Sex, symptoms, extent of radiotherapy, splenectomy, age, and number of MOPP courses were assessed for their impact on ANLL incidence by multivariate analysis.

CONCLUSION

Cox's proportional hazards regression showed that splenectomy and, as previously described by others, the number of courses of MOPP are prognostic factors that increase the risk of secondary ANLL in HD patients treated with combined modality therapy. These data raise interesting questions regarding the possible role of the spleen in leukemia development.
Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.
Authors: Waits T M , Greco F A , Greer J P , Johnson D H , Wolff S N , Stein R S , McMaster M L , Hainsworth J D
Published: February 2017

PURPOSE

Despite substantial advances in the treatment of aggressive non-Hodgkin's lymphoma, therapeutic results with conventional regimens remain poor in some subsets of patients. In an attempt to improve the prognosis of such patients we used an 8-week, multidrug chemotherapy regimen of high dose-intensity.

PATIENTS AND METHODS

Between April 1986 and April 1991, 70 patients with advanced intermediate- or high-grade non-Hodgkin's lymphoma were treated. The median age was 41 years (range, 18 to 69). Fifty-one patients (73%) had stage IV disease; 37 (53%) were Shipp's category 3; 17 (24%) had small noncleaved-cell lymphoma; 35 (50%) had Eastern Cooperative Oncology Group (ECOG) performance status > or = 2; 24 (34%) had two or more extranodal sites involved; and 17 (24%) had bone marrow involvement. The 8-week regimen included cyclophosphamide, etoposide, doxorubicin, vincristine, bleomycin, methotrexate with leucovorin rescue, and prednisone.

RESULTS

Sixty-two of 70 patients completed the regimen as planned. Fifty-seven patients (81%) obtained a complete response (CR) and the actuarial 5-year failure-free survival rate is 52%. Thirty-seven patients remain alive and disease-free a median of 35 months (range, 7 to 68) after therapy. Adverse prognostic factors included age more than 50 years, bone marrow involvement, and serum lactic dehydrogenase (LDH) more than 500 IU/L (normal range, 125 to 250). Myelosuppression was responsible for most of the treatment-related toxicity. Severe leukopenia (< 1,000/microL) occurred in all patients and lasted a median of 9 days. Seven patients (10%) died of myelosuppression-related complications; five of these patients were older than 60 years.

CONCLUSION

This brief but intensive therapy was effective in treating poor-prognosis patients with non-Hodgkin's lymphoma. With this therapy, patients with small noncleaved-cell lymphoma or Shipp's category 3 disease had treatment outcome similar to the group as a whole. This therapy was not well tolerated by patients older than 60 years, and should not be given to this subgroup. Verification of these results in a randomized trial setting is indicated.
Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion.
Authors: Burris H , Irvin R , Kuhn J , Kalter S , Smith L , Shaffer D , Fields S , Weiss G , Eckardt J , Rodriguez G
Published: February 2017

PURPOSE

To determine the potential efficacy and dose-limiting toxicity of taxotere, a hemisynthetic inhibitor of tubulin depolymerization.

PATIENTS AND METHODS

Fifty-eight patients were administered taxotere in this phase I clinical trial as a 6-hour or a 2-hour infusion repeated every 21 days. Forty patients received 181 courses on the 6-hour infusion schedule, and 18 patients received 105 courses on the 2-hour infusion schedule.

RESULTS

Neutropenia was the dose-limiting toxicity on both schedules. The maximally tolerated dose was 100 mg/m2 on the 6-hour infusion schedule and 115 mg/m2 on the 2-hour infusion schedule. The most prominent nonhematologic toxicities included mucositis (more prominent on the 6-hour infusion schedule), transient rash (more common on the 2-hour infusion schedule), and alopecia. Hypersensitivity reactions were seen in five patients. There was no evidence of neurotoxicity or cardiotoxicity. One partial response was noted on the 6-hour infusion schedule (one in refractory breast cancer) and four additional partial responses were noted on the 2-hour infusion schedule (two in adenocarcinoma of the lung, one in refractory breast cancer, one in cholangio-carcinoma). In addition, 10 patients had minor responses. Pharmacokinetic studies showed plasma concentrations of taxotere declined in a triexponential manner, with a terminal half-life of 11.8 hours.

CONCLUSION

The recommended starting dose for phase II taxotere trials is 100 mg/m2 administered as a 2-hour infusion, repeated every 21 days. Taxotere is a promising antineoplastic agent worthy of extensive phase II testing in patients with a variety of malignancies.
Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group.
Authors: Anderson J R , Jenkin R D , Wilson J F , Kjeldsberg C R , Sposto R , Chilcote R R , Coccia P F , Exelby P R , Siegel S , Meadows A T
Published: February 2017

PURPOSE

We analyzed the long-term results of a Childrens Cancer Group (CCG) randomized study comparing cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) versus LSA2L2 as treatment for childhood non-Hodgkin's lymphoma. The initial results were previously reported (N Engl J Med 308:559, 1983).

PATIENTS AND METHODS

A total of 429 patients are reported here, 68 with localized disease and 361 with disseminated disease. The distribution of disseminated-disease patients by histologic type was 164 lymphoblastic, 60 large-cell, and 137 undifferentiated lymphomas. Median follow-up duration of surviving patients is 8 years.

RESULTS

Event-free survival (EFS) of patients with localized disease was 84% at 5 years. No differences were seen between the two treatment regimens. Results for patients with disseminated disease was dependent on histologic subtype: patients with lymphoblastic lymphoma did better when treated with LSA2L2 (5-year EFS of 64% v 35% for COMP); COMP produced better results for patients with undifferentiated lymphoma (5-year EFS of 50% v 29% for LSA2L2). Results for large-cell lymphoma patients were similar (5-year EFS of 52% for COMP v 43% for LSA2L2). Five percent of patients died of treatment-related complications while on therapy (primarily infections). Only four deaths without progression have been observed off-therapy (two from restrictive lung disease, one from an acute asthma attack, one from colon cancer). Patient survival rates after recurrence were poor.

CONCLUSION

Treatment success can be expected in 84% of pediatric patients with localized non-Hodgkin's lymphoma. For patients with disseminated disease, treatment success can be expected in 64% of those with lymphoblastic and 50% of those with undifferentiated or large-cell disease. To date, late adverse events are rare.
Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation.
Authors: Sandoval C , Pui C H , Bowman L C , Heaton D , Hurwitz C A , Raimondi S C , Behm F G , Head D R
Published: February 2017

PURPOSE

Patient records were reviewed to identify cases of secondary acute myeloid leukemia (AML) with clinical and cytogenetic features characteristic of classic epipodophyllotoxin-related AML in patients whose prior treatment for cancer did not include these agents.

PATIENTS AND METHODS

Four cases of secondary AML with chromosomal abnormalities involving bands 11q23 and 21q22, in the absence of prior treatment with etoposide or teniposide, were identified among patients treated at St Jude Children's Research Hospital between January 1980 and April 1992.

RESULTS

The four identified patients were initially treated for rhabdomyosarcoma, non-Hodgkin's lymphoma (n = 2), and Hodgkins' disease. Prior chemotherapy included relatively low cumulative doses of doxorubicin (median, 150 mg/m2; range, 120 to 375 mg/m2) and cyclophosphamide (median, 3,100 mg/m2; range, 2,250 to 11,400 mg/m2). All four patients had received radiation therapy: 59.4 Gy to the right middle ear for rhabdomyosarcoma; 15 Gy and 12 Gy to the abdomen and right lower quadrant, respectively, for non-Hodgkin's lymphoma; 27 Gy to the right orbit for non-Hodgkin's lymphoma; and 36.6 Gy to the mantle-paraaortic-spleen regions plus 20.4 Gy inverted-Y radiation at relapse for Hodgkin's disease. Secondary AML was diagnosed a median of 38 months after initial diagnosis (range, 14 to 55). Leukemic cell translocations involved band 11q23 in two cases and band 21q22 in two. Although all patients obtained a complete remission (CR), only one remains disease-free (at 34 months), following an allogeneic bone marrow transplant.

CONCLUSION

Intercalating topoisomerase II inhibitors (doxorubicin, dactinomycin), when combined with alkylating agents and irradiation, may cause secondary AML.
Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group.
Authors: Amadori S , Testi A M , Aricò M , Comelli A , Giuliano M , Madon E , Masera G , Rondelli R , Zanesco L , Mandelli F
Published: February 2017

PURPOSE

This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission.

PATIENTS AND METHODS

From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles.

RESULTS

Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded.

CONCLUSION

The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.
Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.
Authors: Yahalom J , Gulati S C , Toia M , Maslak P , McCarron E G , O'Brien J P , Portlock C S , Straus D J , Phillips J , Fuks Z
Published: February 2017

PURPOSE

To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD).

PATIENTS AND METHODS

Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months.

RESULTS

Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03).

CONCLUSION

Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.
Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide.
Authors: Wheeler C , Strawderman M , Ayash L , Churchill W H , Bierer B E , Elias A , Gilliland D G , Antman K , Guinan E C , Eder J P
Published: February 2017

PURPOSE

We examined a consecutive series of 78 patients with non-Hodgkin's lymphoma treated on prospective protocols with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) plus autotransplantation to determine prognostic factors for time to treatment failure.

PATIENTS AND METHODS

Patients with relapsed, refractory, or poor-risk intermediate- and high-grade non-Hodgkin's lymphoma were treated with CBV with autologous marrow or peripheral-blood progenitor cell support. Patient characteristics before transplantation were examined in univariate analyses by the log-rank test and simultaneously in a Cox proportional hazards regression analysis. A best-predictive model was determined from those variables significant (P < .10) in the univariate test.

RESULTS

In univariate analysis, intermediate-grade and immunoblastic lymphoma, responsiveness to pretransplant salvage chemotherapy, and transplantation after primary therapy (first complete response [CR] or partial response [PR]) were associated with prolonged time to treatment failure. In proportional hazards multiple regression analysis, intermediate-grade and immunoblastic histology, responsive disease, and autotransplantation in first CR or PR were positive prognostic factors, and these characteristics are the basis of the best-predictive model for prolonged time to failure. Actuarial 3-year failure-free survival of patients with stable or responding disease at autotransplant was 54%.

CONCLUSION

CBV is an effective conditioning regimen in intermediate-grade and immunoblastic non-Hodgkin's lymphoma. Patients with these histologies transplanted while responding to primary therapy, or those with stable disease or disease responding to salvage therapy at the time of autotransplant, are most likely to benefit. Patients with lymphoblastic lymphoma or diffuse undifferentiated lymphoma did poorly with CBV and should be offered alternative therapy.
Postoperative radiation therapy for high-risk colon carcinoma.
Authors: Willett C G , Fung C Y , Kaufman D S , Efird J , Shellito P C
Published: February 2017

PURPOSE

This study examines the experience of patients treated with postoperative radiation therapy after resection of high-risk colon carcinoma in an effort to assess the potential role of this modality in combination with current systemic therapies.

PATIENTS AND METHODS

From 1976 to 1989, 203 patients received postoperative radiation therapy with and without concurrent fluorouracil (5-FU) chemotherapy following resection of modified Astler-Coller B2, B3, C2, and C3 colon tumors. Of the 203 patients, 30 (15%) were identified as having residual local tumor after subtotal resection, whereas 173 (85%) had no known residual disease. The 173 patients treated with adjuvant radiation therapy were compared with a historical control group of 395 patients undergoing surgery only.

RESULTS

Three groups of patients who appeared to benefit from postoperative radiation were identified. Improved local control and recurrence-free survival rates were seen for patients with stage B3 and C3 colon carcinoma treated with postoperative radiation therapy compared with a similarly staged group of patients undergoing surgery only. Irradiated patients whose tumors had an associated abscess or fistula formation had improved local control and recurrence-free survival rates compared with a similar group of patients undergoing surgery only. There appears to be a subset of patients with residual local disease after subtotal resection that may be salvaged by high-dose postoperative radiation therapy.

CONCLUSION

Selected groups of patients with colon carcinoma may benefit from postoperative radiation in addition to current systemic therapies. Integration of 5-FU and levamisole with postoperative radiation therapy should be considered for patients with (1) stage B3 and C3 lesions, (2) tumors associated with abscess or fistula formation, and (3) residual local disease after subtotal resection.
A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients.
Authors: LeVeque F G , Montgomery M , Potter D , Zimmer M B , Rieke J W , Steiger B W , Gallagher S C , Muscoplat C C
Published: February 2017

PURPOSE

To determine the efficacy and safety of pilocarpine hydrochloride for symptomatic relief of postradiation xerostomia symptoms and for saliva production in patients with head and neck cancer.

PATIENTS AND METHODS

One hundred sixty-two head and neck cancer patients who had received at least 40 Gy of radiation (117 patients had received > 60 Gy) with clinically significant xerostomia were enrolled onto a randomized, double-blind, placebo-controlled, multi-center clinical investigation. Patients received 2.5-mg tablets for the first 4 weeks, 5.0-mg tablets for the second 4 weeks, and 10.0-mg tablets for the last 4 weeks of the 12-week study. Patients were allowed to titrate pilocarpine or placebo for improvement in symptoms or to reduce side effects. Patients were evaluated for symptomatic relief by questionnaires and visual analog scales (VAS), and for saliva production by sialometry.

RESULTS

Pilocarpine produced a significant improvement (P = .035) in overall global assessments compared with placebo. There was a statistically significant (P = .020) decreased use of oral comfort agents such as artificial saliva, hard candy, and water. Values for symptomatic improvement in dryness approached significance (P = .057). There were statistically significant postdose improvements in whole and parotid salivary flow in pilocarpine treatment groups versus placebo. All pilocarpine dosages tested were judged to be safe. Adverse experiences were primarily sweating, rhinitis, headache, nausea, and urinary frequency, with the most common side effect being mild to moderate sweating. There were no serious drug-related adverse experiences in any of the pilocarpine treatment groups.

CONCLUSION

It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day.
Rapid administration of multiple cycles of high-dose myelosuppressive chemotherapy in patients with metastatic breast cancer.
Authors: Crown J , Kritz A , Vahdat L , Reich L , Moore M , Hamilton N , Schneider J , Harrison M , Gilewski T , Hudis C
Published: February 2017

PURPOSE

To determine the feasibility and safety of a rapidly cycled sequence of high-dose myelosuppressive chemotherapy courses.

PATIENTS AND METHODS

Seventeen patients with metastatic breast cancer were treated with two courses of cyclophosphamide (CPA; 3.0 g/m2) supported by granulocyte colony-stimulating factor (G-CSF). Following the first CPA treatment, peripheral-blood leukaphereses commenced when the leukocyte count recovered to 1.0 x 10(9)/L. After hematologic recovery from the second dose of CPA, patients were treated with carboplatin 1,500 mg/m2, etoposide 1,200 mg/m2, and CPA 5.0 g/m2 administered over 3 days. The peripheral-blood progenitors (PBPs) were reinfused 3 days later, and G-CSF was recommenced.

RESULTS

All patients received the three courses. The median interval between treatments was 14 days (range, 13 to 21). Sixteen of the 34 courses of CPA resulted in admissions for fever. Following the third course, neutrophil counts recovered to 0.5 x 10(9)/L at a median of 9 days (range, 8 to 18) after PBP reinfusion and platelets recovered to 50 x 10(9)/L at a median of 12 days (range, 9 to 102). There were no treatment-related deaths. Flow-cytometric analysis was performed on the leukapheresis collections of eight patients. Seven patients with at least 2.0 x 10(6) CD34+ CD33- cells per kilogram body weight exhibited prompt hematologic recovery. One patient with 0.03 x 10(6) CD34+ CD33- cells was still cytopenic on day 21, and required reinfusion of her back-up marrow. Among seven patients with measurable or assessable disease, there were two complete responses (CRs) and four partial responses (PRs).

CONCLUSION

These preliminary results suggest that multiple, rapidly cycled courses of high-dose myelosuppressive chemotherapy can be administered. PBPs, harvested during the G-CSF-augmented rebound from CPA-induced cytopenia, produce rapid hematologic recovery in patients undergoing high-dose chemotherapy (HDC). Further follow-up will be necessary to assess the efficacy of this specific regimen in the treatment of metastatic breast cancer.