bluuebunny/crossref_metadata_2025 huggingface dataset:
Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up.
Authors: Roth B J , Greist A , Kubilis P S , Williams S D , Einhorn L H
Published: February 2017

A retrospective analysis of the initial 229 cases of disseminated germ cell tumors treated at Indiana University with cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin revealed 146 patients who are alive and disease-free with a minimum follow-up of 6 years and a median follow-up of 8.5 years. At 12 years, the estimated probability of survival is 65.0%, and the estimated probability of relapse-free survival for complete responders is 83.5%. Long-term complications, such as clinically significant organ toxicity or therapy-related second malignancies, have not been observed. The functional status of survivors is maintained, with 95% returning to their pretherapy status, of which 88% are fully employed. Of patients receiving chemotherapy without abdominal surgery, 35% have fathered healthy children posttherapy. Achievement of complete remission (CR) in disseminated germ cell tumors with cisplatin-based combination chemotherapy translates to long-term disease-free survival and cure for the majority of patients, with preservation of functional status.
Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center.
Authors: Hu E , Hufford S , Lukes R , Bernstein-Singer M , Sobel G , Gill P , Pinter-Brown L , Rarick M , Rosen P , Brynes R
Published: February 2017

The reported experience with Hodgkin's disease (HD) in the United States has come primarily from large referral centers that attract a predominantly white population of high socioeconomic status (SES). The majority of these patients had the nodular sclerosis (NS) histologic subtype and asymptomatic stage I/II disease. We have reviewed the records of 178 patients with HD seen within the past 17 years at Los Angeles County-University of Southern California Medical Center (LAC/USC), which is a nonreferral, government-operated facility. Our patient population was found to be heterogeneous, with 38% white, 22% black, and 36% Hispanic. Systemic "B" symptoms were noted in 62% of patients at diagnosis, and 63% had advanced disease (stage III or IV). NS pathologic subtype was present in only 52% of the group. Comparison between the races revealed: (1) Hispanics had a higher incidence of lymphocyte depleted subtype and less NS than whites (P less than .06); (2) whites had equal distribution between stages I/II and III/IV; (3) blacks and Hispanics presented more frequently with stage III/IV (P = .10); and (4) extranodal involvement occurred most often in bone in whites, and was equally distributed between liver, lung, and bone in blacks and Hispanics. We conclude that the lower SES, mixed racial population seen at our institution more closely resembles the reports of HD in Third-World countries and is characterized by advanced symptomatic disease. Further, the clinical pathologic characteristics of HD in the United States may vary significantly, depending upon the precise ethnic and socioeconomic status of the patients being served.
High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors.
Authors: Slease R B , Benear J B , Selby G B , Reitz C L , Hughes W L , Watkins C L , Epstein R B
Published: February 2017

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.
Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study.
Authors: Rossi A , Molinari R , Boracchi P , Del Vecchio M , Marubini E , Nava M , Morandi L , Zucali R , Pilotti S , Grandi C
Published: February 2017

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.
Stage I nonseminomatous germ cell testicular tumor: prediction of metastatic potential by primary histopathology.
Authors: Fung C Y , Kalish L A , Brodsky G L , Richie J P , Garnick M B
Published: February 2017

A study of 60 patients with clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) was conducted to identify prognostic factors that may predict the likelihood of metastasis. Clinical features and histopathologic features of the primary testicular tumor were examined and analyzed for correlations with the presence of retroperitoneal nodal metastasis documented by surgery (N+) and with development of relapse (R+). Pathologic tumor stage greater than or equal to 2, with tumor extension into the tunica albuginea, rete testis, epididymis, or spermatic cord, was correlated with an increased rate of N+ compared with pathologic tumor stage I (P = .001). Vascular invasion was correlated with a higher rate of N+ (P = .05) and had a similar association with R+ (P = .08). Tumors containing less than 50% teratoma were found to have a higher rate of N+ than tumors with greater than or equal to 50% teratoma (P = .02). Based on the identified prognostic factors, a model for predicting the probability of retroperitoneal nodal metastasis in clinical stage I patients is proposed. The risk factors for nodal metastasis are: pathologic tumor stage greater than or equal to 2, vascular invasion, and less than 50% teratoma. Patients with none of the risk factors are considered at low risk and may be offered orchiectomy alone with surveillance for initial treatment. Patients with all three risk factors are at high risk and should be treated with a retroperitoneal lymph node dissection (RPLND) or possibly chemotherapy. Patients with one or two risk factors are at intermediate risk; it is recommended that they undergo RPLND. This risk model facilitates a rational approach to the management of clinical stage I NSGCT.
Dose-response in the treatment of breast cancer: a critical review.
Authors: Henderson I C , Hayes D F , Gelman R
Published: February 2017

In animal tumor models the dose-response curve for cytotoxic agents, especially cyclophosphamide, may be steep, but the slope and shape of this curve depends not only on the drug used but on the schedule of drug administration, the specific tumor type, tumor cell kinetics, and tumor mass. It might be anticipated from these studies that the human tumors most sensitive to dose effects would be leukemia, lymphoma, small-cell carcinoma of the lung, and testicular tumors rather than the low growth fraction, relatively less responsive tumors such as breast cancer. However, the clinical evidence for a steep dose-response curve in any tumor type is limited. For breast cancer such evidence is largely retrospective or derived from uncontrolled trials. The data available from randomized trials makes it seem unlikely that small, or even moderate, reductions in drug dose for nontrivial reasons will compromise the survival of patients with either early or metastatic disease. In spite of promising data from small trials, there is, as yet, inadequate evidence to justify the use of very-high-dose therapy and autologous marrow transplant outside the setting of a well-designed clinical trial. The value of high-dose therapy, intensive dose rate, and cumulative drug dose should each be studied in randomized controlled trials.
A Cause-Specific Hazard Rate Analysis of Prognostic Factors Among 199 Adults With Acute Lymphoblastic Leukemia
Authors: Gaynor Jeffrey , Chapman Douglass , Little Claudia , McKenzie Susan , Miller Wendy , Andreeff Michael , Arlin Zalmen , Berman Ellin , Kempin Sanford , Gee Timothy , Clarkson Bayard
Published: February 2017

The statement in Table 2 (p 1018) of the article by Gaynor et al published in the June 1988 issue (6:1014–1030), "among factors associated with a shorter remission duration" should have read, "among factors associated with remission duration." The association listed directly below that statement, "high log (WBC) with Null or B cell ALL" should have read, "high log (WBC) with T cell ALL."
Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis.
Authors: Boccadoro M , Marmont F , Tribalto M , Fossati G , Redoglia V , Battaglio S , Massaia M , Gallamini A , Comotti B , Barbui T
Published: February 2017

In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity.
Randomized Trial of Observation Versus Adjuvant Therapy With Cyclophosphamide, Fluorouracil, Prednisone With or Without Tamoxifen Following Mastectomy in Postmenopausal Women With Node-Positive Breast Cancer
Authors: Ingle James N. , Everson Lloyd K. , Wieand H. Sam , Martin J. Kirk , Votava Henry J. , Wold Lester E. , Krook James E. , Cullinan Stephen A. , Paulsen J. Kevin , Twito Donald I. , Ahmann David L. , Foley John F. , Green Stephanie J.
Published: February 2017

In Table 4 of the manuscript by Ingle et al published in the September issue (J Clin Oncol 6:1388–1396, 1988) an error was made in the dosage of tamoxifen. The planned dose should have read 140 mg/wk; the mean dose, 125 mg/wk; and the median dose, 140 mg/wk.
Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up.
Authors: Mendenhall N P , Noyes W D , Million R R
Published: February 2017

Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.
Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.
Authors: Leibenhaut M H , Hoppe R T , Efron B , Halpern J , Nelsen T , Rosenberg S A
Published: February 2017

Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.
A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.
Authors: McGuire W P , Arseneau J , Blessing J A , DiSaia P J , Hatch K D , Given F T , Teng N N , Creasman W T
Published: February 2017

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.
Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma.
Authors: Barlogie B , Velasquez W S , Alexanian R , Cabanillas F
Published: February 2017

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.
A phase I trial of recombinant human tumor necrosis factor and interferon-gamma: effects of combination cytokine administration in vivo.
Authors: Demetri G D , Spriggs D R , Sherman M L , Arthur K A , Imamura K , Kufe D W
Published: February 2017

The combination of tumor necrosis factor (TNF) and interferon-gamma has synergistic bioactivity in numerous preclinical model systems. We have tested this potential synergism in vivo by administration of both cytokines to patients with advanced cancer using overlapping 24-hour continuous intravenous (IV) infusions in a phase I trial. Thirty-six patients were treated with a fixed dose of interferon-gamma (200 micrograms/m2/d) with interpatient dose escalation of TNF (from 5 to 205 micrograms/m2/d). The dose-limiting toxicity at the maximal-tolerated dose (MTD) of TNF (205 micrograms/m2) with interferon-gamma was hypotension. Other toxicities noted included an influenza-like syndrome, transient decreases in circulating leukocyte and platelet counts, subclinical evidence of disseminated intravascular coagulation, and the sporadic occurrence of acute pulmonary toxicity. The recommended phase II dose for this combination schedule is TNF, 136 micrograms/m2, with interferon-gamma, 200 micrograms/m2. The addition of interferon-gamma to TNF resulted in a greater than three-fold increase in toxicity compared with TNF administered as a single agent, supporting the hypothesis that the combination of these cytokines may induce synergistic effects in vivo.
Patterns of Failure Following Local Excision and Local Excision and Postoperative Radiation Therapy for Invasive Rectal Adenocarcinoma
Authors: Willett Christopher G. , Tepper Joel E. , Donnelly Susan , Wood William C. , Shellito Paul C. , Rodkey Grant V. , Stracher Michael A. , Compton Carolyn C.
Published: February 2017

An error was made in the running head of the report "Patterns of Failure Following Local Excision and Local Excision and Postoperative Radiation Therapy for Invasive Rectal Adenocarcinoma" by Willett et al in the August issue (J Clin Oncol 7:1003–1008, 1989). The running head should have read: "Local Excision and Radiotherapy for Rectal Cancer."
Ifosfamide plus doxorubicin in metastatic adult sarcomas: a multi-institutional phase II trial.
Authors: Loehrer P J , Sledge G W , Nicaise C , Usakewicz J , Hainsworth J D , Martelo O J , Omura G , Braun T J
Published: February 2017

Between April 1986 and March 1987, 42 patients with advanced sarcoma were entered in this multi-institutional trial evaluating ifosfamide plus doxorubicin. The majority of patients had leiomyosarcoma and malignant fibrous histiocytoma although two patients with sarcomas of osseous origin were included. Doxorubicin was administered at a dosage of 60 mg/m2 by continuous push and ifosfamide 5.0 g/m2 by continuous infusion over 24 hours with mesna (7.5 g2 over 36 hours) with courses repeated every 3 weeks until progression, toxicity cumulative doxorubicin dosage of 450 mg/m2. Overall, 15 (36%) patients demonstrated objective remissions including three complete and 12 partial remissions (95% confidence limits, 21.5% to 52.0%). The median duration of remission was 7.0 months and the median survival time for all eligible patients was 8.0 months. Toxicity was predominantly hematologic with the median leukocyte nadir being 1,300 per microliter of blood and documented sepsis in six patients. These data support activity for ifosfamide plus doxorubicin in patients with advanced sarcoma, but the actual contribution of ifosfamide needs to be evaluated through prospective randomized trials which are currently underway.
Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone versus metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian Oncology Group for Clinical Research.
Authors: Roila F , Tonato M , Basurto C , Picciafuoco M , Bracarda S , Donati D , Malacarne P , Monici L , Di Costanzo F , Patoia L
Published: February 2017

Despite treatment, emesis remains a major problem with cisplatin (CDDP) chemotherapy. Reasons for variability in antiemetic response among patients and in subsequent cycles are largely unknown and toxicity is sometimes severe. We have, therefore, carried out a multicenter, double-blind randomized trial comparing a combination of high-dose metoclopramide (MTC) (1 mg/kg x 4) and methylprednisolone (P) (treatment A) with a shorter but higher single-dose schedule of metoclopramide (3 mg/kg x 2) combined with dexamethasone (DEX) and diphenhydramine (DIP) to prevent extrapyramidal reactions (treatment B). Three hundred sixty-seven consecutive patients treated with various chemotherapy combinations containing CDDP were studied. Complete protection from vomiting/nausea was, at first cycle, 72.5%/79.5% with treatment B and 55.8%/65.1% with treatment A, a statistically significant difference (P less than .002/P less than .005). In subsequent cycles, protection from emesis significantly decreased with no difference between the two treatments. Multifactorial analysis shows that women, younger patients, outpatients, and patients who experienced emesis in previous cycles were at higher risk of suffering nausea and/or vomiting. Both regimens were well tolerated, but patients treated with treatment B had significantly less extrapyramidal reactions (1.7%/6.1%, P = .053). Treatment B is preferred due to its greater efficacy and lower incidence of extrapyramidal reactions. Trials on antiemetic therapy should take into account the important variables able to influence the efficacy of treatment. There is still a need for improving prevention of emesis in CDDP-treated patients.
Clinical pharmacology of a novel diarylsulfonylurea anticancer agent.
Authors: Taylor C W , Alberts D S , Ketcham M A , Satterlee W G , Holdsworth M T , Plezia P M , Peng Y M , McCloskey T M , Roe D J , Hamilton M
Published: February 2017

LY186641 (diarylsulfonylurea, [DSU]) is a novel anticancer agent because of its unique diarylsulfonylurea chemical structure, broad-spectrum antisolid-tumor activity in preclinical models, presumed novel mechanism of action and preclinical toxicities of methemoglobinemia (Met Hgb) and decreased red blood cell (RBC) survival. In this study, the in vitro drug sensitivity of human tumors as well as clinical pharmacology and toxicology of DSU in patients with cancer were examined. DSU was administered orally, daily for 7 days with a 3-week treatment cycle. Dose-limiting toxicities were Met Hgb and RBC hemolysis. The maximum-tolerated dose was found to be 1,200 mg/m2/d for 7 days. In pharmacokinetic studies, DSU was found to have a prolonged serum half-life (approximately 30 hours) and a large area under the plasma disappearance curve (8,883.3 micrograms.hr/mL at 1,200 mg/m2/d). A partial remission was observed in one patient with refractory ovarian cancer. In conclusion, DSU can be safely administered to cancer patients and does display antitumor activity. Potential means of obviating the toxicities of this compound are discussed.
A Rational Next Step in the Treatment of Some Rectal Adenocarcinomas
Authors: Steele Glenn , Hamilton J. Michael , Karr James P.
Published: February 2017

A sentence in the last paragraph on page 989 of the editorial "A Rational Next Step in the Treatment of Some Rectal Adenocarcinomas" by Steele et al (J Clin Oncol 7:988–990, 1989) contained several errors. It should have read: "However, given the improbability of any randomized trial being performed, one alternative is the formation of a multiinstitutional treatment plan in which patients with T1 or T2N0M0 distal rectal adenocarcinomas accrue to a single treatment arm in which adequate local resection is followed in the patients with T2 primaries (who have a 10% to 30% chance of insidious microscopic perirectal nodal disease) with the best presently available adjuvant treatment."
Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.
Authors: Miller D R , Coccia P F , Bleyer W A , Lukens J N , Siegel S E , Sather H N , Hammond G D
Published: February 2017

The Childrens Cancer Study Group (CCSG) CCG-160 protocol series was designed to evaluate prognostic factors in acute lymphoblastic leukemia (ALL). Patients were assigned to one of three prognostic groups based upon initial WBC count and age. To determine the optimal duration of therapy, CCG-160 patients completing 2 years of treatment in continuous remission were randomized ("late randomization") to discontinue therapy or receive another year of maintenance therapy. The prognostic significance of early response to induction therapy, as measured by the percentage of lymphoblasts in the day-14 bone marrow (d14 BM) aspirate, was evaluated in 2,516 children. For 1,490 patients with complete data, the status of the d 14 BM was a highly significant predictor of disease-free survival (DFS) by univariate and multivariate analysis (P less than .0001). The observed/expected (O/E) failure rate in patients with d14 M1 (less than 5% blasts), M2 (4% to 25% blasts), or M3 (greater than 25% blasts) BM rating who were subsequently M1 on day 28 or day 42, was .87, 1.59, and 2.30, respectively (P less than .0001). Patients with M2 or M3 d14 BM were more likely to have L2 ALL (modified French-American-British [FAB] morphologic classification), P less than .001. The significance of the d14 BM rating persisted after correction was made for WBC count and clinical prognostic groups using current CCSG criteria, except in infants less than 12 months of age. The d14 BM was also the most significant predictor of DFS in 975 patients after late randomization at 2 years following diagnosis. The O/E failure rate in patients with d14 M1, M2, or M3 BM was .88, 1.78, and 2.02, respectively (P = .0002, trend). Other significant predictors of late relapse were prognostic groups (P = .0003, trend) and initial WBC count (P = .004, trend). Predictive for both early and late relapse of ALL, early response should be monitored closely and alternative treatment regimens should be considered for slow responders.
High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.
Authors: Williams S F , Mick R , Desser R , Golick J , Beschorner J , Bitran J D
Published: February 2017

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.
Intraarterial cisplatin and concurrent radiation for locally advanced bladder cancer.
Authors: Eapen L , Stewart D , Danjoux C , Genest P , Futter N , Moors D , Irvine A , Crook J , Aitken S , Gerig L
Published: February 2017

Between 1983 and 1987 25 patients with invasive bladder cancer (16 stage tumor 3 (T3) and nine stage T4) were treated with intraarterial cisplatin and concurrent radical radiation (20/25) or intraarterial cisplatin, concurrent preoperative radiation, and cystectomy (5/25). One patient died from treatment-related toxicity. Other toxicities have been what one would expect from the individual treatment modalities except for a sensory sacral root neuropathy in 11 of 24 (46%) patients. Twenty-three of 24 (96%) patients achieved a complete response (CR) and the projected actuarial 2-year survival is 90%. Only one of the 23 complete responders has had an invasive local recurrence. The excellent complete local response and survival rates achieved warrant further study of the combination of intraarterial cisplatin and radiation as a bladder-preserving strategy.
Cisplatin, fluorouracil with leucovorin calcium enhancement, and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer: a phase II study.
Authors: Wendt T G , Hartenstein R C , Wustrow T P , Lissner J
Published: February 2017

In a phase II study, patients with locally advanced squamous cell carcinoma of the head and neck were treated with simultaneous chemoradiotherapy. Treatment was divided into three courses. Chemotherapy consisted of cis-diamminedichloroplatinum (II) (cisplatin [cis-DDP]) 60 mg/m2 intravenously (IV), fluorouracil (5-FUra) 350 mg/m2 IV, and folinic acid (leucovorin calcium [FA]) 50 mg/m2 IV on day 2 as bolus, and 5-FUra 350 mg/m2 over 24 hours and FA 100 mg/m2 over 24 hours on days 2 through 5. Radiotherapy consisted of 23.4 Gy over nine days divided into 13 fractions of 1.8 Gy each delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy over 51 days. Between August 1984 and October 1986, 62 (modified AJCC stage III, four; IV A, eight; IV B, 50) consecutive patients were entered in the study. Three patients died during treatment due to tumor hemorrhage. Of 59 patients, 48 (81%) achieved a clinically complete response (cCR); 11 (19%) achieved a partial response (cPR). Mean follow-up of the surviving patients was 29+ (24 to 44) months. Actuarial 2-year survival probability is 52%, including three early deaths from tumor bleeding. Tumor and neck nodes control rates at 2 years were 92% for stage III and IV A patients and 65% for stage IV B patients. Patients with cCR had a significantly better 2-year tumor and neck nodes control probability compared with patients who achieved cPR after therapy (P less than .001). Six patients developed distant metastases. Overall toxicity was tolerable, mucositis particularly was not a limiting factor.
Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study.
Authors: Rezkalla S , Kloner R A , Ensley J , al-Sarraf M , Revels S , Olivenstein A , Bhasin S , Kerpel-Fronious S , Turi Z G
Published: February 2017

Although there have been anecdotal reports of cardiac toxicity associated with fluorouracil (5-FU) therapy, this phenomenon has not been studied in a systematic fashion. We prospectively performed continuous ambulatory ECG monitoring on 25 patients undergoing 5-FU infusion for treatment of solid tumors in order to assess the incidence of ischemic ST changes. Patients were monitored for 23 +/- 4 hours before 5-FU infusion, and 98 +/- 9 hours during 5-FU infusion. Anginal episodes were rare: only one patient had angina (during 5-FU infusion). However, asymptomatic ST changes (greater than or equal to 1 mm ST deviation) were common: six of 25 patients (24%) had ST changes before 5-FU infusion v 17 (68%) during 5-FU infusion (P less than .002). The incidence of ischemic episodes per patient per hour was 0.05 +/- 0.02 prior to 5-FU infusion v 0.13 +/- 0.03 during 5-FU infusion (P less than .001); the duration of ECG changes was 0.6 +/- 0.3 minutes per patient per hour before 5-FU v 1.9 +/- 0.5 minutes per patient per hour during 5-FU (P less than .01). ECG changes were more common among patients with known coronary artery disease. There were two cases of sudden death, both of which occurred at the end of the chemotherapy course. We conclude that 5-FU infusion is associated with a significant increase in silent ST segment deviation suggestive of ischemia, particularly among patients with coronary artery disease. The mechanism and clinical significance of these ECG changes remain to be determined.
MOPP chemotherapy versus extended-field radiotherapy in the management of pathological stages I-IIA Hodgkin's disease.
Authors: Cimino G , Biti G P , Anselmo A P , Maurizi Enrici R , Bellesi G P , Bosi A , Cionini L , Mungai V , Papa G , Ponticelli P
Published: February 2017

In order to assess whether mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (CT), which is less expensive and more easily available than radiotherapy (RT), is at least as effective as RT in terms of cure rate and has less iatrogenic damage, 89 consecutive patients with Hodgkin's disease (HD) (pathological stage I-IIA) were randomly allocated to receive mantle plus lumbar bar RT (36-45 Gy) or CT (six courses of MOPP). Forty-five patients were entered in the RT group and 44 in the CT group. The median follow-up was 60 months. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 patients in the CT group. Overall survival (OS) and disease-free survival (DFS) were, respectively, 87.2% and 72.7% in the CT group and 93.5% and 74% in the RT group. Survival probability of relapsing patients was 76% for the patients in the RT group and 45% in the CT group. Treatment-related complications were more severe in the CT group as compared with the RT group.
Six-year results of the Eastern Cooperative Oncology Group trial of observation versus CMFP versus CMFPT in postmenopausal patients with node-positive breast cancer.
Authors: Taylor S G , Knuiman M W , Sleeper L A , Olson J E , Tormey D C , Gilchrist K W , Falkson G , Rosenthal S N , Carbone P P , Cummings F J
Published: February 2017

The Eastern Cooperative Oncology Group (ECOG) trial of adjuvant cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen (CMFPT) for 1 year compared with observation alone in 265 postmenopausal patients with node-positive breast cancer is reported with 74 months median follow-up. Overall relapse-free survival tended to favor CMFPT (P = .08), but no survival differences existed between any treatment group. The addition of tamoxifen to CMFP led to slightly (but not significantly) better relapse-free status in all subgroups analyzed. Subgroup analysis based on stratification variables showed significant benefit from CMFP (+/- T) only in estrogen receptor (ER)-negative patients with respect to disease-free status (P = .0003), but not survival (P = .54). Relapse-free status was actually worse for CMFP-treated patients with ER-positive tumors, but not significantly so (P = .15). By multivariate analysis other significant risk factors for relapse-free status were primary tumor size, number of nodes pathologically involved, and the number of nodes examined. ER status was prognostic only for the observation group with the benefit from chemotherapy on ER-negative patients obliterating this difference in treated patients. Survival was affected by the number of involved nodes, tumor size, presence of tumor necrosis, and patient obesity. Analysis of toxicity showed elevation of liver enzymes during the first year to be more common in the observation group compared with those patients receiving adjuvant treatment and to be associated with early recurrence. Toxicity from adjuvant treatment persisted beyond termination of therapy in 53% of patients, but was usually mild and self-limited. We conclude CMFPT offers relapse-free survival benefit in ER-negative patients, but the value of chemotherapy in ER-positive postmenopausal, node-positive patients must be questioned.
Measuring quality of life in cancer patients.
Authors: Donovan K , Sanson-Fisher R W , Redman S
Published: February 2017

The diagnosis and management of cancer can have a major impact on every aspect of a patient's quality of life. Despite its importance, quality of life is rarely a reported outcome in randomized clinical trials in cancer patients. Failure to collect quality-of-life information may reflect a lack of information among researchers and clinicians about the adequacy and relative merits of measures available for assessing quality of life. We reviewed the adequacy of the 17 existing scales for assessing quality of life in cancer patients against characteristics needed for an adequate measure. None of the existing measures met all of the criteria. Recommendations about the relative adequacy of existing scales were made.
Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21.
Authors: O'Brien S , Kantarjian H M , Keating M , Gagnon G , Cork A , Trujillo J , McCredie K B
Published: February 2017

Forty-three patients with acute myelogenous leukemia (AML) and a translocation 8;21 were reviewed. The patients' median age was 30 years, and 62% were men. Twenty-three patients (53%) had loss of a sex chromosome and ten (23%) had other chromosomal abnormalities in addition to the 8;21 translocation. Complete remission (CR) with induction chemotherapy was achieved in 40 patients (93%). The median CR duration was 18 months (range, 1 to 137+ months). Median survival time was 17 months (range, 0.5 to 138+ months) with a 3-year survival rate of 31%. Twenty-three patients (53%) relapsed between 1 and 58 months after entering remission with reinduction therapy resulting in 8 CRs (35%). Thirteen characteristics were examined for an effect on survival. The most striking finding was a significant association between elevated absolute granulocyte count and poor survival (P = .002). WBC count greater than 10,000/microL was also associated with shorter survival (P = .05). Patient age, albumin level, and platelet count showed trends for survival association. Although patients with AML and t(8;21) are regarded as a favorable group with respect to survival, we found a subset of patients who do very poorly. Intensive or more investigational approaches in first remission should be considered for these patients.
High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.
Authors: Trump D L , Havlin K H , Messing E M , Cummings K B , Lange P H , Jordan V C
Published: February 2017

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.
A Phase I Clinical and Pharmacokinetic Study of Carboplatin and Autologous Bone Marrow Support
Authors: Shea Thomas C. , Flaherty Mary , Elias Anthony , Eder Joseph P. , Antman Karen , Begg Colin , Schnipper Lowell , Frei Emil , Henner William D.
Published: February 2017

The key to Fig 1 in the report by Shea et al published in the May issue (J Clin Oncol 7:651–661, 1989) contained several errors. It is reprinted here correctly with the figure in its entirety.

Please see the PDF for Figure.
Myelodysplastic syndrome and acute nonlymphocytic leukemia secondary to mitolactol treatment in patients with breast cancer.
Authors: Falkson G , Gelman R S , Dreicer R , Tormey D C , Alberts A S , Coccia-Portugal M A , Rushing D , Bennett J M
Published: February 2017

One thousand four hundred sixty patients with 2,590 patient-years of follow-up were treated on 15 protocols for metastatic breast cancer with dibromodulcitol (mitolactol; DBD)-containing regimens since 1976. Twenty-three patients developed myelodysplastic syndrome (MDS) and/or acute nonlymphocytic leukemia (ANLL). The overall risk of developing MDS or ANLL per person is 1.6%. In patients who had received more than 16,000 mg of DBD the risk per person is 6%, and in the high-dose subsets of patients who received no prior radiation or alkylator therapy, it is 7.9%. The risk per person increases to a maximum by 30 to 36 months (5.3%). The high risk was seen despite a study population of metastatic breast cancer patients with a median survival of 16 months. This analysis strongly suggests that DBD is one of the most potent of the reported leukemogenic-inducing agents. Further use of this drug in both the adjuvant and metastatic situation should be reconsidered.
Phase II trial of carboplatin in the management of malignant mesothelioma.
Authors: Raghavan D , Gianoutsos P , Bishop J , Lee J , Young I , Corte P , Bye P , McCaughan B
Published: February 2017

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.