bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer.
Authors: Butler R W , Hill J M , Steinherz P G , Meyers P A , Finlay J L
Published: February 2017

PURPOSE

To investigate the neuropsychologic effects of cranial irradiation (CRT), intrathecal methotrexate (IT-MTX), and systemic methotrexate (SYS-MTX) in a cohort of pediatric patients with cancer who had either received no, moderate, or high doses of these treatments alone or in various combinations.

PATIENT AND METHODS

Data were collected on 120 pediatric cancer patients from a large variety of diagnostic groups. Patients completed a comprehensive neuropsychologic test battery designed to assess most areas of cognitive functioning. In analyzing cancer treatment effects, the following variables were statistically controlled: (1) age, (2) socioeconomic status (SES), (3) age at diagnosis, (4) months since both onset and cessation of CNS treatments, (5) time missed from schooling, and (6) presence/type of CNS cancer.

RESULTS

CRT, largely in combination with IT-MTX, was significantly associated with deficits in several, primarily nondominant, hemispheric neuropsychologic functions, even after control and other treatment variables were addressed. This relationship was somewhat, but not highly, dose-dependent at CRT doses greater than approximately 18 Gy, at least over the first several years posttreatment. While there was statistically significant evidence for cognitive impairment, absence from school during treatment and age at diagnosis were more predictive of reading and spelling academic achievement than having received CRT. IT-MTX and SYS-MTX alone were not associated with significant degrees of neuropsychologic involvement.

CONCLUSION

CRT, especially when administered with IT-MTX, at currently used dosages was associated with significant neuropsychologic impairment in children. These impairments are most likely to be reflected in nonverbal intelligence, perceptual abilities, and susceptibility to distraction. IT-MTX and SYS-MTX did not result in a consistent pattern of cognitive deficit.
European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion.
Authors: Eisenhauer E A , ten Bokkel Huinink W W , Swenerton K D , Gianni L , Myles J , van der Burg M E , Kerr I , Vermorken J B , Buser K , Colombo N
Published: February 2017

PURPOSE

Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication.

METHODS

Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival.

RESULTS

Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted.

CONCLUSION

The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.
VAD-PECC regimen in the treatment of advanced-stage multiple myeloma.
Authors: Delain M , Linassier C , Petitdidier C , Goupille P , Luthier F , Combe M , Reisenleiter M , Benboubker L , Lamagnère J P , Colombat P
Published: February 2017

PURPOSE

This prospective study was undertaken to evaluate the efficacy of combination chemotherapy with alternating cycles of vincristine, doxorubicin, and dexamethasone (VAD) and prednisone, vindesine, carmustine, and cyclophosphamide (PECC) in poor-risk multiple myeloma (MM).

PATIENTS AND METHODS

Forty-four patients were previously untreated; 36 had been pretreated with an alkylating agent-containing regimen and had refractory or relapsed MM. All previously untreated patients had a high tumor burden at inclusion (stage III according to the Durie and Salmon classification). Logistic regression and the Cox proportional hazards models were used to assess the association between patient characteristics and response rate and survival, respectively.

RESULTS

The overall response rate was 68% for previously untreated patients, compared with 54% for previously treated patients (P = .16). The median survival time for all patients was 28 months: 53 months in previously untreated patients, and 18 months in previously treated patients. Univariate analysis showed that the predictive factors that had a significant affect on survival in the newly diagnosed patients were age, therapeutic response to VAD-PECC, low pretreatment Karnofsky score, high baseline serum beta 2-microglobulin (beta 2M) level, bone marrow impairment, and renal insufficiency at the start of treatment. When these parameters were used as continuous variables in multivariate analysis, three were found to correlate with survival: serum beta 2M, followed by therapeutic response and Karnofsky score. In the previously treated group, only Karnofsky score entered the Cox model.

CONCLUSION

These results indicate that combination VAD-PECC chemotherapy is an effective treatment that results in high response rates and long-term survival in advanced MM.
Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British National Lymphoma Investigation pilot study.
Authors: Bates N P , Williams M V , Bessell E M , Vaughan Hudson G , Vaughan Hudson B
Published: February 2017

PURPOSE

To assess the efficacy and toxicity of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease.

PATIENTS AND METHODS

Thirty eligible patients with clinical stage IA or IIA Hodgkin's disease, at intermediate risk of relapse, were enrolled into a prospective multicenter pilot study. They received two cycles of VBM chemotherapy, followed by involved-field radiotherapy and then four further cycles of VBM. The median follow-up duration from the start of treatment is 30 months.

RESULTS

All 26 patients with assessable disease showed an objective response after two cycles of VBM (nine complete responses, 17 partial responses). By the completion of treatment, 27 patients were in complete remission; two had stable residual masses, which have not progressed at 26 and 34 months of follow-up; and one patient who died of treatment-related sepsis was in complete remission at that time. Two relapses have occurred, 19 and 28 months after starting VBM. Cough and dyspnea developed in 14 of 30 patients, and were associated with impairment of pulmonary function tests. Three episodes of neutropenic sepsis were recorded.

CONCLUSION

VBM with involved-field radiotherapy is an effective treatment for early Hodgkin's disease. However, the associated toxicity, both pulmonary and hematologic, is severe, making the regimen unsuitable for routine use.
Evaluation of the extent of lymphadenectomy in a randomized trial of Western- versus Japanese-type surgery in gastric cancer.
Authors: Bunt A M , Hermans J , Boon M C , van de Velde C J , Sasako M , Fleuren G J , Bruijn J A
Published: February 2017

PURPOSE

In the context of a prospective, randomized trial of gastric cancer treatment, comparing Western surgical resection with limited lymphadenectomy (R1) versus Japanese surgical resection with extended lymphadenectomy (R2), we analyzed adherence to the specified surgical-pathologic guidelines.

PATIENTS AND METHODS

Following evaluation of 389 patients, we quantified noncompliance (ie, performance of less dissection than specified) and contamination (ie, performance of more extensive dissection than specified). Of 389 patients, pathologic data permitted identification of 237 eligible patients treated with curative intent.

RESULTS

Noncompliance occurred in 84% of R1 and R2 cases, with magnitude significantly (P < .001) higher in R2 cases versus R1 cases. Contamination occurred in 48% of R1 cases and 52% of R2 cases, with the magnitude of contamination moderate and equally distributed between the two groups. The contamination in R1 resections and the noncompliance in R2 resections lead to a partial homogenization of the groups, undermining the likelihood of detecting any potential therapeutic advantage to R2 dissection.

CONCLUSION

The observed tendency to perform R1 resections combined with insufficient retrieval of lymph nodes underlines the need for increased surgical-pathologic standardization in this trial. Potential remedies are discussed. Proper conduct of clinical trials requires reliable means of standardizing performance of the surgical-pathologic team, an elusive but important goal.
Technetium 99m-labeled IMMU-4, a monoclonal antibody against carcinoembryonic antigen, for imaging of occult recurrent colorectal cancer in patients with rising serum carcinoembryonic antigen levels.
Authors: Patt Y Z , Podoloff D A , Curley S , Kasi L , Smith R , Bhadkamkar V , Charnsangavej C
Published: February 2017

PURPOSE

We tested whether nuclear imaging with technetium 99m-labeled murine monoclonal antibody (MoAb) against carcinoembryonic antigen (CEA) IMMU-4 will detect recurrent colorectal disease in patients with a rising serum CEA level but negative abdominal and pelvic computed tomographic (CT) scan, chest radiograph, and colonoscopy, or barium enema.

PATIENTS AND METHODS

Sixteen patients with completely resected, CEA-producing colorectal cancer were given 1 mg of 99mTc-labeled IMMU-4 intravenously with no toxic side effects. Planar and single-photon emission CT (SPECT) scans were acquired at 6 hours. Fifteen patients underwent an exploratory laparotomy at 24 hours. Results of the scintigraphy were correlated with surgical findings.

RESULTS

Twelve of 15 patients (80%) had true-positive (TP) scans when correlated with surgery. Two of 15 (13%) had true-negative (TN) scans inasmuch as exploratory laparotomy failed to detect recurrent disease. A false-positive (FP) scan was obtained in one of 15 (7%). There were no false-negative (FN) scans. Sensitivity, specificity, accuracy, and the positive predictive value (PPV) were 100%, 67%, 93%, and 92%, respectively. Twenty-six histologically confirmed areas of malignancy were found and correlated with areas of increased activity seen on IMMU-4 scintigraphy. Twenty-one were TP; five were not detected by scintigraphy and were thus considered to be FN. There were five FP lesions and 25 TN regions. Sensitivity, specificity, accuracy, and the PPV in these 26 cancer tissues were 81%, 83%, 82%, and 81%, respectively. The median radioactivity ratio of tumorous tissue to normal tissue was 3.33, with a range of 0.89 to 17.16.

CONCLUSIONS

These results suggest that 99mTc IMMU-4 scintigraphy is an important addition to the armamentarium available for diagnostic imaging and may help detect occult metastatic cancer missed by abdominal and pelvic CT in patients with rising CEA levels.
Risk factors in breast-conservation therapy.
Authors: Borger J , Kemperman H , Hart A , Peterse H , van Dongen J , Bartelink H
Published: February 2017

PURPOSE

To identify clinical and pathologic factors associated with an increased risk of local recurrence following breast-conservation therapy (BCT) to assess the safety of this procedure for all subgroups of patients.

PATIENTS AND METHODS

The study population consisted of 1,026 patients with clinical stage I and II breast cancer treated between 1979 and 1988 at the Netherlands Cancer Institute. The BCT regimen consisted of local excision and axillary lymph node dissection (ALND) followed by whole-breast irradiation to a total dose of 50 Gy in 2-Gy fractions and boost irradiation (mostly by iridium implant) of 15 to 25 Gy.

RESULTS

With a median follow-up duration of 66 months, the actuarial breast recurrence rate was 4% at 5 years, counting all breast recurrences. Univariate analysis showed seven factors to be associated with an increased risk of local recurrence; age, residual tumor at reexcision, histologic tumor type, presence of any carcinoma-in-situ component, vascular invasion, microscopic margin involvement, and whole-breast radiation dose. Three factors remained independently significant after proportional hazard regression analysis: age, margin involvement, and the presence of vascular invasion. When the analysis was repeated, but counting only those breast recurrences that occurred before regional or distant failures, only young age and vascular invasion were independent predictive factors. In the third analysis, factors predicting the necessity of local salvage treatment were analyzed. In this analysis, the possible bias in the former analysis caused by censoring actuarial methods was avoided. The results were the same as in the second analysis, showing young age and vascular invasion as the only independent predictive factors. Breast recurrence rates were 6% for patients less than 40 years of age and 8% for patients with tumors showing vascular invasion. In the absence of risk factors, the breast recurrence rate is only 1% at 5 years.

CONCLUSION

Slightly higher recurrence rates were found in patients less than 40 years of age and in patients with tumors showing vascular invasion. The role of margin involvement is uncertain.
Proliferating cell nuclear antigen and mitotic activity in rectal cancer: predictor of response to preoperative irradiation.
Authors: Willett C G , Warland G , Cheek R , Coen J , Efird J , Shellito P C , Compton C C
Published: February 2017

PURPOSE

This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by proliferating cell nuclear antigen (PCNA) and mitotic activity.

PATIENTS AND METHODS

Ninety patients with clinical stage T3 and T4 rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for PCNA activity (number of tumor cells staining immunohistochemically with an anti-PCNA monoclonal antibody) and the number of mitoses per 10 high-powered fields (hpf). Postirradiation surgical specimens were examined for extent of residual disease.

RESULTS

The tumors of 33 of 90 patients (37%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were independently associated with the likelihood of marked pathologic regression after preoperative irradiation: lesion size and PCNA/mitotic activity. When stratified by tumor size, marked tumor regression occurred most frequently in smaller tumors with high PCNA/mitotic activity compared with larger tumors with lower PCNA/mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate PCNA/mitotic activity.

CONCLUSION

Tumor PCNA/mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.
Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.
Authors: Williams S , Blessing J A , Liao S Y , Ball H , Hanjani P
Published: February 2017

PURPOSE

This study was performed to determine the effectiveness of postoperative adjuvant chemotherapy in patients with surgically resected ovarian germ cell tumors.

PATIENTS AND METHODS

After tumor removal and thorough surgical staging, patients were enrolled on this study and treated with three courses of cisplatin, etoposide, and bleomycin (BEP). Reassessment laparotomy was required of consenting, appropriate patients initially, but became an optional procedure in 1989.

RESULTS

Of 93 patients assessable on this trial, 89 are continuously free of germ cell cancer. At second-look laparotomy, two other patients were found to have small foci of immature teratoma; both remain clinically free of recurrence. One received subsequent alternate chemotherapy and one did not. Thus, 91 of 93 patients are currently free of germ cell cancer. Follow-up duration ranges from 4.0 to 90.3 months, with 67 patients monitored for longer than 2 years. Acute toxicity was moderate. One patient developed acute myelomonocytic leukemia 22 months after diagnosis. Another patient was noted to have a malignant lymphoma 69 months after protocol treatment.

CONCLUSION

Three courses of BEP will nearly always prevent recurrence in well-staged patients with completely resected ovarian germ cell tumors and should be given to all such patients. The development of acute leukemia as a complication of treatment is disturbing and mandates careful long-term follow-up, but is unusual and does not alter the risk-to-benefit ratio of treatment.
2-Chlorodeoxyadenosine is an active salvage therapy in advanced indolent non-Hodgkin's lymphoma.
Authors: Hoffman M , Tallman M S , Hakimian D , Janson D , Hogan D , Variakogis D , Kuzel T , Gordon L I , Rai K
Published: February 2017

PURPOSE

To determine the response rate to 2-chlorodeoxyadenosine (2-CdA; cladribine) in patients with advanced indolent non-Hodgkin's lymphoma (NHL) who fail to respond to or progress after a response to standard chemotherapy drugs.

PATIENTS AND METHODS

Twenty-one patients were treated with at least one cycle of 2-CdA 0.1 mg/kg/d by continuous infusion for 5 or 7 days.

RESULTS

The overall response rate (complete response [CR] and partial response [PR]) was nine of 21 patients (43%; 95% confidence interval, 22% to 64%). Unmaintained durable responses (longest follow-up, 29+ months) have been observed. The treatment was well tolerated by all patients. The major toxicity was related to myelosuppression (predominantly neutropenia) and immunosuppression with infection.

CONCLUSION

The purine analog 2-CdA is an active salvage therapy in pretreated patients with indolent NHL, and deserves further assessment in untreated patients and in combination with other chemotherapy agents.
Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside.
Authors: Livingston P O , Wong G Y , Adluri S , Tao Y , Padavan M , Parente R , Hanlon C , Calves M J , Helling F , Ritter G
Published: February 2017

PURPOSE

To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction.

PATIENTS AND METHODS

One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy).

RESULTS

GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance.

CONCLUSION

(1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.
Significance of a partial or slow response to front-line chemotherapy in the management of intermediate-grade or high-grade non-Hodgkin's lymphoma: a literature review.
Authors: Haw R , Sawka C A , Franssen E , Berinstein N L
Published: February 2017

PURPOSE

The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients.

METHODS

A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed.

RESULTS

The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies.

CONCLUSION

Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.
Tumor Epidermal Growth Factor Receptor Studies in Patients With Non-Small-Cell Lung Cancer or Head and Neck Cancer Treated With Monoclonal Antibody RG 83852
Authors: Perez-Soler Roman , Donato Nicholas J. , Shin Dong M. , Rosenblum Michael G. , Zhang Hua-Zhong , Tornos Carmen , Brewer Hanna , Chan James C. , Lee Jin Soo , Hong Waun K. , Murray James L.
Published: February 2017

The Acknowledgment regarding the report "Tumor Epidermal Growth Factor Receptor Studies in Patients With Non-Small-Cell Lung Cancer or Head and Neck Cancer Treated With Monoclonal Antibody RG 83852" (J Clin Oncol 12:730–739, 1994) should have read as follows:

"We thank Dr Chris Tarr, Rhône-Poulenc/Rorer, and Dr Jon Holmlund, National Cancer Institute, for supplying RG 83852; Trupti Shah, Lora B. Thompson, Margaret Janus, Marc Lewis, and M. Perez for skillful technical assistance; and Kevin Flynn for editorial assistance."
Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma.
Authors: Haas R , Moos M , Karcher A , Möhle R , Witt B , Goldschmidt H , Frühauf S , Flentje M , Wannenmacher M , Hunstein W
Published: February 2017

PURPOSE

To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma.

PATIENTS AND METHODS

Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM).

RESULTS

A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available.

CONCLUSION

Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.
Development of a simplified single-apheresis approach for peripheral-blood progenitor-cell transplantation in previously treated patients with lymphoma.
Authors: Jones H M , Jones S A , Watts M J , Khwaja A , Mills W , Fielding A , Goldstone A H , Linch D C
Published: February 2017

PURPOSE

The aims of this study were to develop a simplified, safe, and cost-effective peripheral-blood progenitor-cell (PBPC) mobilization protocol.

PATIENTS AND METHODS

Twenty-six patients with relapsed or resistant lymphomas were entered onto a sequential cohort study in which schedules of various granulocyte colony-stimulating factor (G-CSF) were administered after cyclophosphamide 1.5 g/m2. Hematologic recovery after high-dose carmustine (BCNU) etoposide, cytarabine, and melphalan (BEAM) chemotherapy was compared with that of 46 patients who received autologous bone marrow transplantation (ABMT) without growth factors and 28 patients who received ABMT followed by G-CSF.

RESULTS

When G-CSF (10 micrograms/kg/d) was administered from the day after the cyclophosphamide, neutropenia developed on day 8 followed by an abrupt increase in the WBC count. The optimal time for PBPC harvesting was the day on which the postnadir WBC count was greater than 8.0 x 10(9)/L, as shown by CD34+ cell counts and granulocytic-macrophage colony-forming cell (GM-CFC) assays. The reproducibility of the response was such that routine monitoring of CD34+ cell counts and GM-CFC was not necessary. A single leukapheresis on this day was adequate for prompt hematologic engraftment, and posttransplant G-CSF made little further impact on the rapid recovery. Compared with both control groups, the use of PBPC led to more rapid neutrophil recovery, markedly accelerated platelet recovery, less use of antimicrobial agents and parenteral nutrition, and more than 10 days earlier discharge from hospital. All of these differences were highly significant (P < .01).

CONCLUSION

A simplified mobilization protocol is described that requires only one apheresis to achieve rapid hematologic engraftment.
A decade of breast cancer clinical investigation: results as reported in the Program/Proceedings of the American Society of Clinical Oncology.
Authors: Chlebowski R T , Lillington L M
Published: February 2017

PURPOSE

To test the hypothesis that clinical research results have driven changes in recent breast cancer management recommendations.

METHODS

All breast cancer abstracts in the Program/Proceedings of the American Society of Clinical Oncology (ASCO) from 1984 to 1993 were prospectively reviewed in 31 areas and categorized by study type, study question, whether statistical significance was claimed, and whether the abstract was presented.

RESULTS

Of 1,372 abstracts, 54% reported on prospective clinical trials (PCTs) and 17% on randomized clinical trials (RCTs). The total number of published abstracts progressively increased (from 87 in 1984 to 221 in 1993) and author citations nearly quadrupled (from 430 in 1984 to 1,642 in 1993, P < .01); however, RCTs have come to represent a smaller proportion of reports: 37% (33 of 89) in 1986 versus 10% (22 of 221) in 1993 (P < .001). The size of adjuvant-therapy RCTs has progressively increased (mean +/- SEM subjects/trial, 237 +/- 43 in 1984 to 874 +/- 374 in 1993), but has remained small in advanced-disease RCTs (mean +/- SEM subjects/trial, 145 +/- 25 in 1984 to 146 +/- 34 in 1993). For adjuvant therapy, 14 of 90 RCTs (with 51,207 patients) reported a significant (P < .05) survival benefit for investigational therapies (16%). For advanced-disease therapy, only three of 141 RCTs (with 26,281 patients) reported a significant (P < .05) survival benefit for investigational therapies (2%). Randomization was rarely used in trials of dose-intensity with blood-product support (zero of 86 trials) or locally advanced disease.

CONCLUSION

For breast cancer ASCO abstracts in the past decade, we determined the following: (1) adjuvant trials have not infrequently supported study hypotheses; and (2) advanced-disease trials have consistently failed to identify new approaches with a significant impact on survival. These results suggest that a critical process evaluation of current policy and procedures involved in directing breast cancer research is warranted, especially for strategies in advanced disease.
Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies.
Authors: Stahel R A , Jost L M , Cerny T , Pichert G , Honegger H , Tobler A , Jacky E , Fey M , Platzer E
Published: February 2017

PURPOSE

The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT).

PATIENTS AND METHODS

Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT.

RESULTS

For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients.

CONCLUSION

Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.
Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma.
Authors: Moulopoulos L A , Dimopoulos M A , Smith T L , Weber D M , Delasalle K B , Libshitz H I , Alexanian R
Published: February 2017

PURPOSE

To assess the prognostic significance of magnetic resonance (MR) imaging in patients with newly diagnosed asymptomatic multiple myeloma.

PATIENTS AND METHODS

Thirty-eight consecutive patients with asymptomatic myeloma of low tumor mass and negative skeletal surveys underwent MR imaging of the thoracic and lumbosacral spine. The presence and patterns of marrow involvement were correlated with standard laboratory parameters and time to disease progression.

RESULTS

Nineteen patients (50%) had evidence of marrow involvement at spinal MR imaging. MR patterns of marrow involvement were classified as diffuse (five patients), variegated (nine), and focal (five). Patients with abnormal MR imaging studies required therapy after a median of 16 months, versus 43 months for those with normal MR studies (P < .01).

CONCLUSION

Abnormal marrow patterns were present in half of patients with asymptomatic myeloma. An abnormal MR study of the spine identified asymptomatic patients who were likely to require treatment earlier than those with a normal MR study. A normal MR pattern provided additional justification to defer institution of chemotherapy. However, MR imaging remains an investigational tool to stage patients with multiple myeloma until more data are accumulated.
Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.
Authors: Cascinu S , Cordella L , Del Ferro E , Fronzoni M , Catalano G
Published: February 2017

PURPOSE

We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity.

PATIENTS AND METHODS

Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment.

RESULTS

At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH.

CONCLUSION

This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.
Ten-year results of a randomized trial evaluating prolonged low-dose adjuvant chemotherapy in node-positive breast cancer: a joint European Organization for Research and Treatment of Cancer-Dutch Breast Cancer Working Party Study. Cooperating Investigators.
Authors: Clahsen P C , van de Velde C J , Welvaart K , van Driel O J , Sylvester R J
Published: February 2017

PURPOSE

To investigate whether treatment with prolonged low-dose adjuvant chemotherapy could improve survival of patients with axillary node-positive breast cancer.

PATIENTS AND METHODS

Four hundred fifty-two patients with axillary node-positive breast cancer who received postoperative irradiation were prospectively randomized in a trial (European Organization for Research and Treatment of Cancer [EORTC] 09771) that compared surgery followed by prolonged low-dose chemotherapy versus surgery alone. Chemotherapy was given for a period of 2 years and consisted of monthly courses of cyclophosphamide 50 mg/m2 orally on days 1 to 14, methotrexate 15 mg/m2 intravenously on days 1 and 8, and fluorouracil 350 mg/m2 intravenously on days 1 and 8 (CMF).

RESULTS

At a median follow-up time of 10 years, the overall survival duration was significantly prolonged in the chemotherapy arm (hazards ratio, 0.75; 95% confidence interval, 0.56 to 0.99; P = .04). Ten-year overall survival rates (+/- SE) were 59% (+/- 3.6%) for the chemotherapy arm and 50% (+/- 3.7%) for the control arm. Time to local relapse was significantly prolonged in the chemotherapy arm (hazards ratio, 0.63; 95% confidence interval, 0.42 to 0.94; P = .02). Patients with one to three positive axillary nodes and patients with estrogen receptor-negative tumors especially benefited from chemotherapy. Toxicity was observed in 93% of patients.

CONCLUSION

We conclude that prolonged low-dose adjuvant CMF can significantly prolong overall survival in patients with node-positive breast cancer. However, considering the fact that toxicity was still considerable despite reducing the dose of chemotherapy by 50%, we believe that conventionally dosed short-term regimens are preferable in the treatment of node-positive breast cancer.
Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy.
Authors: Couzi R J , Helzlsouer K J , Fetting J H
Published: February 2017

PURPOSE

To determine the prevalence and severity of vasomotor, gynecologic, and other symptoms among breast cancer patients, their health concerns, beliefs about estrogen replacement therapy (ERT), and willingness to take estrogen under medical supervision.

MATERIALS AND METHODS

A questionnaire was mailed to 320 women aged 40 to 65 years and diagnosed with in situ or invasive locoregional breast cancer in the years 1988 to 1992.

RESULTS

Of 222 eligible respondents, 190 were postmenopausal. The prevalence of symptoms among the postmenopausal women was as follows: hot flashes, 65%; night sweats, 44%; vaginal dryness, 48%; dyspareunia, 26%; difficulty sleeping, 44%; and feeling depressed, 44%. The latter two symptoms increased in frequency with increasing severity of vasomotor symptoms (P for trend < or = .001). Forty-one percent of menopausal women perceived that they had experienced, since their breast cancer diagnosis, a physical or emotional problem related to menopause. Of these women, 50% felt they needed treatment. Overall, 31% of postmenopausal women would consider taking estrogen. Those who perceived that they had experienced a menopausal problem were more likely to consider estrogen than those who did not (42% v 22%, P = .003). The proportions willing to take estrogen increased with increasing severity of symptoms, particularly feelings of depression and sleep disturbance (P for trend = .008 and .007, respectively). Awareness that estrogen decreases the risks of heart disease and osteoporosis was not associated with an increased willingness to take it. However, beliefs that estrogen increases the risks of recurrent breast cancer and uterine cancer were associated with a decreased willingness to take it (P = .003 and .08, respectively).

CONCLUSION

Vasomotor symptoms have a significant impact on the quality of life of breast cancer patients. Clinical trials to determine the safest and the most effective ways to relieve these symptoms are needed.
Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas.
Authors: Mohiuddin M , Regine W F , Stevens J , Rosato F , Barbot D , Biermann W , Cantor R
Published: February 2017

PURPOSE

To evaluate the effectiveness of combined intraoperative radiation therapy (IORT) and perioperative chemotherapy in the management of unresectable pancreatic cancer.

MATERIALS AND METHODS

Forty-nine patients with localized unresectable adenocarcinoma of the pancreas were treated in a multimodality program of initial IORT and perioperative chemotherapy (fluorouracil [5-FU]/leucovorin) followed by combined external-beam radiation (40 to 55 Gy) and continued chemotherapy. Patients were evaluated for toxicity, pattern of failure, and survival. The follow-up times of these patients range from a minimum of 12 months to a maximum of 62 months, with a median of 28 months.

RESULTS

The incidence of perioperative mortality was 0%. Early postsurgical morbidity (grade 3/4) was observed in seven of 49 patients (14%) and late treatment-related morbidity (grade 3/4) in eight of 43 patients (19%) alive beyond 6 months. Morbidity was primarily gastrointestinal (GI), with no hematologic toxicities observed. The median survival time in the total group of patients is 16 months, with a 2-year survival rate of 22% and a 4-year survival rate of 7%. Freedom from local progression of disease was achieved in 71% of patients.

CONCLUSION

The patients who undergo IORT with electrons and treated with perioperative chemotherapy (5-FU leucovorin) followed by additional external-beam radiation and chemotherapy appear to have improved survival, with few early or late complications. Dose escalation of external-beam radiation and chemotherapy may further improve local control of disease and survival of patients.
Phase I feasibility and pharmacologic study of weekly intraperitoneal paclitaxel: a Gynecologic Oncology Group pilot Study.
Authors: Francis P , Rowinsky E , Schneider J , Hakes T , Hoskins W , Markman M
Published: February 2017

PURPOSE

This study was designed to define the maximum-tolerated dose (MTD) and pharmacology of paclitaxel administered by the intraperitoneal (IP) route on a weekly schedule.

PATIENTS AND METHODS

Thirty-three patients with residual ovarian cancer following standard chemotherapy were entered onto this phase I trial. Patients were treated weekly with IP paclitaxel administered in 2 L of normal saline following premedication. Patients with nonassessable disease received 16 weekly courses. The initial dose level was 20 mg/m2/wk. There was no intrapatient dose escalation.

RESULTS

Multiple grade 2 toxicities were observed at the 75-mg/m2/wk dose level. These toxicities included abdominal pain, nausea, vomiting, leukopenia, and fatigue. One episode of grade 4 vomiting thought to be secondary to a transient partial small-bowel obstruction occurred at this dose level. At dose levels > or = 60 to 65 mg/m2, pharmacology studies documented the persistence of significant IP paclitaxel levels 1 week after drug administration, suggesting very slow peritoneal clearance and continuous exposure of the peritoneal cavity to active concentrations of paclitaxel. Low plasma paclitaxel concentrations were detected in the majority of patients treated at dose levels > or = 55 mg/m2.

CONCLUSION

Paclitaxel can be delivered by the IP route on a weekly schedule with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The recommended dose and schedule for phase II study of IP paclitaxel is 60 to 65 mg/m2 weekly.
Bone marrow involvement in Hodgkin's disease: an analysis of 135 consecutive cases. German Hodgkin's Lymphoma Study Group.
Authors: Munker R , Hasenclever D , Brosteanu O , Hiller E , Diehl V
Published: February 2017

PURPOSE

To describe the incidence of primary bone marrow involvement (BMI) in Hodgkin's disease (HD) and its correlation with clinical and laboratory features present at diagnosis, and to evaluate the prognostic relevance of BMI.

PATIENTS AND METHODS

Between 1983 and 1991, 2,307 patients with HD were treated according to two trial generations (HD1-3 and HD4-6) of the German Hodgkin's Lymphoma Study Group (GHSG).

RESULTS

One hundred thirty-five cases of primary BMI were observed. The incidence of BMI was 4.8% in the HD4-6 study generation, which included all stages. Among stage IV patients, 32% had BMI. Among those with BMI, other organs were also involved in 33%. Among all patients, the presence of BMI was significantly associated with B symptoms, lymph nodes on both sides of the diaphragm, mixed cellularity histologic subtype, leukocytopenia, anemia, thrombocytopenia, lactate dehydrogenase (LDH) level more than 400 U/L, and erythrocyte sedimentation rate (ESR) more than 40 mm/h. BMI was negatively correlated with a large mediastinal tumor (3.7% v 20.0% in non-BMI cases). Eighty-seven of 108 (81%) assessable patients with BMI achieved a complete remission (CR). This compares favorably with the overall CR rate in all stage IIIB/IV patients. Among stage IV patients, BMI has no prognostic relevance with regard to freedom from treatment failure and overall survival. Twenty-one patients with BMI relapsed after having achieved a CR. Only five of these (24%) again had a positive bone marrow biopsy.

CONCLUSION

The prognosis of patients with BMI is not worse than the prognosis of other advanced-stage HD patients. BMI alone does not define a special high-risk group in which a different treatment approach is indicated.