bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy.
Authors: Coia L R , Engstrom P F , Paul A
Published: February 2017

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.
A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma.
Authors: Ernstoff M S , Trautman T , Davis C A , Reich S D , Witman P , Balser J , Rudnick S , Kirkwood J M
Published: February 2017

Thirty patients with documented metastatic melanoma were randomly assigned to receive recombinant DNA-produced gamma-interferon (specific activity approximately, 20 MU/mg) intravenously (IV) over either two or 24 hours at dosages of 3, 30, 300, 1,000, or 3,000 micrograms/m2. Objective toxicity resembled that of alpha-interferon and included fever, chills, myalgias, headache, and fatigue. Neutropenia, elevations in liver enzymes, tachyarrhythmias, and CNS changes also were noted. Dose-limiting toxicity included neutropenia, liver enzyme abnormality, constitutional symptoms, and a change in mental status. The incidence of toxicity was qualitatively similar in both two- and 24-hour treatment arms, but was quantitatively more severe in the 24-hour continuous infusion arm. Maximum tolerated dose was 1,000 micrograms/m2 in both schedules. Pharmacokinetic studies showed a half-life of six to nine hours. One patient had a complete response after two cycles of therapy and an additional patient entered partial remission after three cycles. Recombinant gamma-interferon (rIRN-gamma) is tolerated at dosages of 1,000 micrograms/m2 administered daily either by two or 24 hour infusion for 14 days in patients with metastatic melanoma. The responses documented in this early trial warrant further evaluation for the treatment of metastatic melanoma.
Radiotherapy with curative intent: an option in selected patients relapsing after chemotherapy for advanced Hodgkin's disease.
Authors: Roach M , Kapp D S , Rosenberg S A , Hoppe R T
Published: February 2017

Thirteen patients who had relapsed or failed to obtain a complete remission after combination chemotherapy for the treatment of advanced Hodgkin's disease were treated with subtotal or total lymphoid irradiation with curative intent. Twelve of the 13 patients achieved a complete response (CR). Five of the 12 CRs subsequently relapsed at 3, 9, 9, 12, and 19 months. One patient died of leukemia 11 months following radiotherapy. The actuarial relapse-free survival at 1 year was 60%, and six patients (50%) remain disease-free with a median follow-up of 34 months (range, 10 to 115 months) following the completion of radiotherapy. Patients who failed to obtain a CR to their initial chemotherapy, whose chemotherapy CR was of short duration, or who relapsed initially in extranodal sites, tended to have a worse outcome with radiotherapy. Patients who had long disease-free intervals after initial chemotherapy or relapsed only in nodal sites tended to do relatively well. Radiation therapy was well tolerated with no major toxicity. Potentially curative radiation therapy should be considered an option in the management of selected patients who relapse following combination chemotherapy for advanced Hodgkin's disease.
WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma.
Authors: Glover D , Glick J H , Weiler C , Fox K , Guerry D
Published: February 2017

Cisplatin, alone or in combination with other chemotherapeutic agents, is relatively inactive against metastatic melanoma. Prior trials have demonstrated partial response (PR) rates of less than 10% with cisplatin alone. WR-2721 is an organic thiophosphate compound, which in the animal model, selectively protects normal tissues against the toxicity of cisplatin chemotherapy. During the course of a phase I trial of WR-2721 and cisplatin, objective PRs were noted in patients with far advanced metastatic melanoma. These observations led us to perform a phase II trial of WR-2721 and cisplatin. Thirty-six patients received 128 courses of WR-2721 before cisplatin (60 to 150 mg/m2). All patients had progressive disease before treatment. Objective PRs were observed in 19 of 36 evaluable patients (53%). Three additional patients had minor responses (MRs). PRs occurred in 53% of patients with prior chemotherapy (ten of 19). Sites of responding metastases were subcutaneous disease (15 of 19 patients), lymph nodes (16 of 21 patients), lung (four of ten patients), and liver (eight of 17 patients). The median duration of response was 4 months, with a mean of 4.5 months (range, 1 to 8 months). Transient nephrotoxicity was observed in less than 5% of courses. In all cases, renal function returned to normal within 1 to 2 weeks. Hematologic toxicity was mild and infrequent. Nine patients developed peripheral neuropathy following a median cisplatin dose of 670 mg/m2. Twenty patients experienced mild clinical hearing loss. These data suggest that WR-2721 may potentiate the antitumor activity of cisplatin in metastatic melanoma.
The efficacy of mesna (2-mercaptoethane sodium sulfonate) as a uroprotectant in patients with hemorrhagic cystitis receiving further oxazaphosphorine chemotherapy.
Authors: Andriole G L , Sandlund J T , Miser J S , Arasi V , Linehan M , Magrath I T
Published: February 2017

We examined the possibility of continuing oxazaphosphorine therapy in patients with previously documented cyclophosphamide- or ifosfamide-induced hematuria by concomitant use of the uroprotective agent, mesna. Twenty-six patients with oxazaphosphorine-induced hematuria received additional cyclophosphamide or ifosfamide with mesna. Twelve, who had previously experienced hematuria with ifosfamide, received a median of 3.5 more cycles of ifosfamide/mesna. One patient developed further hematuria (grade 1). Of seven patients who experienced acute hematuria with cyclophosphamide, one experienced further hematuria after an additional course of cyclophosphamide with mesna, but none of the other six patients developed further hematuria when administered either cyclophosphamide/mesna (two) or ifosfamide/mesna (four). Seven patients who had chronic cyclophosphamide-induced hematuria had further oxazaphosphorine with mesna without worsening of their hematuria. Mesna is an effective uroprotective agent that prevents recurrent acute hemorrhagic cystitis, or worsening of chronic hemorrhagic cystitis, in patients receiving further oxazaphosphorine after previous ifosfamide- or cyclophosphamide-induced hematuria.
Analysis of postoperative radiation therapy in stage I through III epithelial ovarian carcinoma.
Authors: Fuller D B , Sause W T , Plenk H P , Menlove R L
Published: February 2017

A retrospective long-term analysis of the results of primary postoperative radiotherapy in 106 women with invasive epithelial ovarian carcinoma is presented. Forty-two women received open-field total abdominopelvic irradiation, and 64 received treatment by various subtotal abdominopelvic techniques. The mean follow-up of living patients in the two groups is 86 and 116 months, respectively. Women who had Federation International Gynecology and Oncology (FIGO) stages I through III-A with no postoperative residual disease, or less than 0.5-cm abdominal and/or less than 2-cm pelvic residual disease formed a favorable group in whom total abdominopelvic irradiation resulted in a 71% 10-year actuarial relapse-free survival rate compared with 40% for those treated by subtotal abdominopelvic techniques (P less than or equal to .0205). The survival improvement due to the total abdominopelvic technique in favorable patients became even more significant (P less than or equal to 0.003) after adjusting for differences in stage, grade, and postoperative residual disease volume (no, or favorable, gross). Increasing grade appeared to be associated with decreasing survival even among favorable patients treated with the optimal technique, although the differences did not approach statistical significance after adjusting for residual disease volume and stage. Surgical bowel complications were equivalent, 7.1% for total abdominopelvic v 8.1% for subtotal abdominopelvic techniques. The addition of intraperitoneal radioactive chromic phosphate increased the surgical bowel complication rate 33% over external pelvic irradiation alone without improving survival. Patients with unfavorable gross residual disease and/or FIGO stages III-B and IV were incurable by any radiation technique. Those with no, or favorable, gross residual tumor constitute a group in whom we believe open-field total abdominopelvic irradiation represents a potentially curative therapy modality.
Primary chemotherapy for clinical stage II nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients.
Authors: Logothetis C J , Swanson D A , Dexeus F , Chong C , Ogden S , Ayala A G , von Eschenbach A C , Johnson D E , Samuels M L
Published: February 2017

Fifty patients with clinical stage II nonseminomatous germ cell tumor of the testis (NSGCTT) were treated with primary chemotherapy followed by a retroperitoneal lymph node dissection (RPLND) in selected patients. The study population included 34 patients with retroperitoneal masses and elevated levels of serum biomarkers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [BHCG] ), five with needle aspiration biopsy-proven retroperitoneal metastases but normal levels of biomarkers, and 11 in whom there were rising levels of serum biomarkers but no radiographic evidence of retroperitoneal metastases. Forty-eight patients (96%) achieved a complete response (CR), with a mean disease-free survival of 132 weeks (range, 55 to 273 weeks). Two patients developed recurrent disease. One died and one achieved a second CR with further therapy (48 + weeks). Postchemotherapy RPLND was required in 11 patients (22%). Patients with embryonal carcinoma had a lower frequency of RPLND (8%) than patients with teratomatous elements in their primary tumor [36%, P = .014]. To reduce the frequency of double therapy (surgery +/- chemotherapy), we propose individualized therapy. Patients presenting with clinical stage II embryonal carcinoma of the testis should receive primary chemotherapy. Patients with clinical stage II NSGCTT and teratomatous elements in their primary tumor continue to require an RPLND. Those patients with intermediate volume disease (greater than 2 cm less than or equal to 5 cm in maximum diameter) may be treated with an RPLND only. Patients with higher volume teratomatous elements (greater than 5 cm less than or equal to 10 cm in maximum diameter) are likely to require the combination of chemotherapy and surgery.
Acute leukemia during pregnancy: the Toronto Leukemia Study Group experience with long-term follow-up of children exposed in utero to chemotherapeutic agents.
Authors: Reynoso E E , Shepherd F A , Messner H A , Farquharson H A , Garvey M B , Baker M A
Published: February 2017

The incidence of acute leukemia in pregnancy is low and even referral centers have limited experience. Although the short-term risks for children exposed in utero to cytotoxic agents are predictable, there is no information on long-term complications. We report here our experience in the treatment of seven cases of acute leukemia diagnosed during pregnancy, and a literature review of 51 cases published since 1975. Fifty-three patients received chemotherapy during their pregnancies. Forty-nine of the 58 cases resulted in the birth of 50 live infants. Twenty-eight infants were born prematurely, and four had low birth-weights for their gestational age. Thirty-three percent of the newborns exposed to chemotherapy in the last month of pregnancy were cytopenic at birth, but other perinatal complications were not increased. Only one child (present series) had obvious congenital malformations, and this same infant later developed a neuroblastoma arising in the adrenal gland and a papillary carcinoma of the thyroid. Follow-up data are not provided in most previously reported cases, but long-term follow-up of our cases from 1 to 17 years has shown normal growth and development and no further malignancies. A central registry is strongly advised in order to document the long-term complications arising in children exposed to chemotherapy in utero.
Chemotherapy for adenocarcinoma of the lung (WHO III): A randomized study of vindesine versus lomustine, cyclophosphamide, and methotrexate versus all four drugs.
Authors: Sørensen J B , Hansen H H , Dombernowsky P , Bork E , Malmberg R , Aabo K , Bødker B , Hansen M
Published: February 2017

Two hundred seventy-nine patients with previously untreated nonresectable adenocarcinoma of the lung (ACL) entered a prospective randomized trial, comparing vindesine (VDS) to a combination of lomustine (CCNU), cyclophosphamide (CTX), and methotrexate (MTX), and to a regimen including all four drugs. Response assessment was possible in 218 patients, while 259 were evaluable for survival. Response rates were similar (22%, 23%, and 27%, respectively) as were median durations of response (15 weeks overall) and survival (29 weeks overall). Patients with dose-limiting toxicity had significantly higher response rate and longer survival than patients without toxicity. The major toxicity was peripheral neuropathy with VDS treatment and myelosuppression with the other two regimens. The VDS single-agent activity in ACL was confirmed, but addition of VDS to the three-drug regimen did not increase activity. Future studies of VDS in combination with other active agents, and comparison to a matched control group on supportive care, are indicated.
Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.
Authors: Hartmann O , Benhamou E , Beaujean F , Kalifa C , Lejars O , Patte C , Behard C , Flamant F , Thyss A , Deville A
Published: February 2017

Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy.
Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma.
Authors: Wiernik P H , Schwartz E L , Einzig A , Strauman J J , Lipton R B , Dutcher J P
Published: February 2017

Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and less than 5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma.
Intranasal buserelin in the treatment of advanced prostatic cancer: a phase II trial.
Authors: Falkson G , Vorobiof D A
Published: February 2017

Thirty-five patients with advanced prostatic cancer were entered in a trial of nasally administered gonadotropin-releasing hormone analogue agonist (GnRHA) buserelin. Four patients were unevaluable for response and toxicity. Twenty-five patients responded to treatment, two with complete remissions, 12 with partial remissions, and 11 who improved. The median baseline value for testosterone was 14.4 nmol/L. After 1 week of treatment, the median value was 10.8 nmol/L, while after 1 month the median value had decreased to 1.1 nmol/L (normal, 10.0 to 34.7). It is concluded that intranasal buserelin is an effective, simple, and safe method to achieve androgen deprivation in the treatment of advanced prostate cancer and is an alternative to orchiectomy and more acceptable than daily subcutaneous injections.
A phase I and pharmacokinetic study with 21-day continuous infusion of epirubicin.
Authors: de Vries E G , Greidanus J , Mulder N H , Nieweg M B , Postmus P E , Schipper D L , Sleijfer D T , Uges D R , Willemse P H
Published: February 2017

A phase I study with continuous administration of epirubicin for 21 days using a venous access port and a portable pump was performed. The first dose step was 2 mg/m2/d for 21 days. Interval between courses was 3 weeks. Dose increment per step was 1 mg/m2/d. Twenty-two patients entered the study and received a total of 58 courses with a median of two (range, one to nine). Up to 5 mg/m2/d no toxicity (according to World Health Organization [WHO] criteria) occurred. At 6 mg/m2/d (six pts), one patient had leukopenia grade 3. Two others had some hair loss. At 7 mg/m2/d (four patients), all patients developed mucositis (two grade 3). Three patients had bone marrow depression (one grade 3 anemia, one grade 4 leukocytopenia), and one patient developed the hand-foot syndrome. No other toxicity occurred in the patients. One patient obtained a partial response (18 weeks), ten had stable disease (12 to 54 weeks), seven had progressive disease, and four were not evaluable for response. One patient developed cellulitis around the port, responding to antibiotic treatment; one patient developed a vena cava superior syndrome that resolved with urokinase and removal of the access port. No septicemia occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with fluorometric detection. Plasma steady state was reached after 57 hours. During steady state there was a linear relationship between epirubicin dose administered and epirubicin level in plasma (r = .58, P less than .05), whole blood (r = .75, P less than .005), and in leukocytes (r = .68, P less than .05). The area under the curve in leukocytes was higher with continuous infusion of 6 mg/m2 for 21 days compared with bolus injection of 80 mg/m2. This method of continuous infusion with epirubicin may be a way to increase intracellular drug-uptake as expressed by intracellular area under curve (AUC). We recommend 6 mg/m2/d for 3 weeks for evaluation of antitumor efficacy in phase II studies.
Very-high-dose cisplatin and etoposide in children with untreated advanced neuroblastoma.
Authors: Hartmann O , Pinkerton C R , Philip T , Zucker J M , Breatnach F
Published: February 2017

Between January and December 1985, 17 children with advanced neuroblastoma who were greater than 1 year old (16 stage IV, one stage III) were administered cisplatin (CPDD, 200 mg/m2) and etoposide (VP-16, 500 mg/m2) as a pilot study of toxicity and response rates for the European Neuroblastoma Study Group (ENSG). The study was designed to assess toxicity of two courses of treatment, and evaluate response rates after this short therapy. The creatinine clearance declined in seven of 15 patients. No patient experienced clinically significant hearing loss, but formal audiometric assessment of nine children revealed characteristic high tone loss in seven patients. Peripheral neuropathy was not seen. Asymptomatic hypomagnesemia (less than 0.7 microEq/L) was frequent, despite routine supplementation. Asymptomatic electrolyte imbalances occurred frequently, but were generally transient. Myelosuppression was severe, but brief. Seven patients required platelet transfusions and seven were readmitted between courses due to febrile episodes while neutropenic. There were no treatment-related deaths. According to strictly defined criteria, 12 of 17 patients showed a partial response (PR), and extensive marrow evaluation showed complete clearing of disease in six of 15 patients. This high-dose regimen, if carefully supervised, is associated with acceptable toxicity, comparable to that seen when the dose of CPDD is spread over several months. The rapidity and degree of response was encouraging and merits further evaluation.
Phase II study of iproplatin in advanced ovarian carcinoma.
Authors: Sessa C , Vermorken J , Renard J , Kaye S , Smith D , ten Bokkel Huinink W , Cavalli F , Pinedo H
Published: February 2017

Iproplatin (cis-dichloro-trans dihydroxy-bis-isopropyl-amine platinum [IV]; CHIP) was administered intravenously (IV) at monthly intervals at doses of 300 mg/m2 and 240 mg/m2 to ten previously untreated and 97 previously treated patients with advanced ovarian carcinoma. The overall response rate was 78% among patients with no prior chemotherapy, 42% among patients with prior chemotherapy not including cisplatin, and 22% among patients with prior chemotherapy including cisplatin. Overall response rates to iproplatin were 6.4% and 54% in patients with/without clinical evidence of tumor resistance to cisplatin. Thrombocytopenia was the dose-limiting toxicity, median time to nadir and to recovery being 2 and 4 weeks, respectively. Patients who had received prior chemotherapy regimens for greater than 1 year showed a 10% greater reduction in platelet count (mean platelet nadir +/- SD, 57.5 +/- 49.96 X 10(3)/microL) and a higher incidence of grade 3 to 4 thrombocytopenia after the first cycle than patients who had received prior chemotherapy regimens for less than 1 year (94.7 +/- 65.99 X 10(3)/microL) Moderate to severe vomiting and diarrhea occurred in 84% and 16% of patients pretreated with chemotherapy. Neuropathy (6%) was reported only in patients with prior cisplatin treatment. Mild and reversible renal toxicity was observed in 6% of cases. Iproplatin is an active drug in ovarian cancer; the results achieved in patients previously treated with cisplatin strongly suggest that the two drugs are cross-resistant.
Keeping up with the cancer literature--PDQ ACCESS.
Authors: Perry D J , Sloane E M , Hubbard S M , Tingley D E , DeVita V T
Published: February 2017

Physician Data Query (PDQ) (National Cancer Institute [NCI], Bethesda, MD) and CANCERLIT (NCI, Bethesda, MD) are two online cancer information databases. PDQ summarizes current cancer therapy literature into specific treatment recommendations. CANCERLIT is a bibliographic system similar to MEDLINE (National Library of Medicine [NLM], Bethesda, MD) that provides a comprehensive source of literature citations for the field of cancer. In this report, we discuss linking PDQ and CANCERLIT with PDQ ACCESS (NCI, Bethesda, MD)--a custom software package that makes searching the cancer literature easy for the practicing physician unfamiliar with database searching.
Use of routine chest radiography in the evaluation of fever in neutropenic pediatric oncology patients.
Authors: Feusner J , Cohen R , O'Leary M , Beach B
Published: February 2017

Evaluation of febrile episodes in children who have become neutropenic during treatment for malignant disease has traditionally included radiography of the chest. It has been our impression that the yield of such examination is low. To test this hypothesis we reviewed all chest radiographs (CXRs) obtained in the above setting in our institution over the last 3 years. These radiographs were independently reviewed by two of us (R.C., J.F.). Sixty-one patients experienced 134 febrile neutropenic episodes for which a CXR was obtained. Only eight (6%) of these films revealed any abnormality. After careful review it was apparent that four of these radiographs did not represent a infectious process. Thus only four of 134 films (2.9%) indicated pulmonary infection as the probable cause of fever in the patient. All four of these patients had prominent respiratory signs or symptoms. Of patients who were febrile but without pulmonary signs/symptoms, only one of 49 had an abnormal radiograph. We feel that such a low yield (at most 2%) calls into question the routine practice of obtaining a CXR in the febrile neutropenic child who is otherwise asymptomatic.
The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma.
Authors: Vose J M , Armitage J O , Weisenburger D D , Bierman P J , Sorensen S , Hutchins M , Moravec D F , Howe D , Dowling M D , Mailliard J
Published: February 2017

Non-Hodgkin's lymphoma (NHL) is a malignancy that occurs frequently in the elderly with a median age greater than 60 years. However, most chemotherapy trials have included predominantly patients less than 60 years of age. We treated 157 patients with diffuse aggressive NHL between September 1982 and May 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), procarbazine, bleomycin, vincristine, and prednisone (CAP/BOP). There were no treatment exclusions for age. Patients in this study ranged in age from 15 to 91 years (median, 63) with 112 patients greater than or equal to 60 years of age. The overall complete remission (CR) rate was 65% with no significant difference for age less than 60 (76%) v age greater than or equal to 60 (61%) (P = .18). With a median 36-month follow-up (range, 22 to 65 months), the overall 5-year survival was 42%. The patients less than 60 years old had a 62% 5-year survival in contrast to a 34% 5-year survival in those patients greater than or equal to age 60 (P = .01). The deaths attributed to tumor or treatment-related toxicity were similar above and below age 60. The difference in survival was due to other causes of death not obviously related to the lymphoma or its therapy-occurring in 22% of patients greater than or equal to 60 years of age but only 2% of patients less than 60 years (P = .005). Our data supports the position that aggressive NHL in elderly patients is not significantly less responsive than in younger patients; however, the inclusion of older patients in clinical trials will decrease the overall survival secondary to deaths due to apparently unrelated causes.
Successful treatment of pure endodermal sinus tumors in adult men.
Authors: Chong C D , Logothetis C J , von Eschenbach A C , Ayala A G , Samuels M L
Published: February 2017

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.
High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia.
Authors: Riddell S , Appelbaum F R , Buckner C D , Stewart P , Clift R , Sanders J , Storb R , Sullivan K , Thomas E D
Published: February 2017

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.
Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia.
Authors: Cassileth P A , Harrington D P , Hines J D , Oken M M , Mazza J J , McGlave P , Bennett J M , O'Connell M J
Published: February 2017

The value of maintenance therapy after the achievement of complete remission in adult acute nonlymphocytic leukemia (ANLL) has never been clearly established. A randomized Eastern Cooperative Oncology Group (ECOG) study of postremission therapy compared outcomes in patients who received no further therapy to those administered long-term maintenance chemotherapy. Adverse results in the group administered no further therapy led to early termination of this trial after only 51 patients were randomized. Patients receiving no postremission therapy experienced significantly inferior remission durations (P = .002) compared with patients receiving maintenance therapy. All 26 patients in the group administered no postremission therapy have relapsed, with a median duration of remission of 4.1 months. In contrast, four of 25 patients (16%) who received maintenance therapy remain disease free, with a median duration of remission of 8.1 months.
Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.
Authors: Prosnitz L R , Farber L R , Kapp D S , Scott J , Bertino J R , Fischer J J , Cadman E C
Published: February 2017

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.
Clinical stage I carcinoma of the testis: a review.
Authors: Fung C Y , Garnick M B
Published: February 2017

Significant advances in the management of disseminated carcinoma of the testis have had a tremendous influence on the management of all stages of disease, including both stage I and stage II. Because the disease is so uniformly curable in advanced forms, strategies have evolved for lower stages of disease to maximize curative potential with minimization of therapeutic intervention and potential long-term side effects. This review addresses issues of diagnosis and initial clinical staging of patients with stage I carcinoma of the testis. The usefulness of biological tumor markers and the accuracy, sensitivity, and specificity of radiographic imaging modalities are emphasized. The traditional treatment of stage I seminomas and nonseminomas includes the role of both radiation therapy and retroperitoneal lymph node dissection (RPLND). Treatment results and complications of each modality are also reviewed. The importance of orchiectomy followed by meticulous surveillance, as well as a critical analysis of prognostic features of subsequent locoregional or systemic relapse in patients with stage I testis cancer, focuses attention on changing concepts of this disease. The rationale underlying improved ability to stage patients meticulously and offer therapeutic intervention when necessary following orchiectomy, constitutes the focus of present and future clinical research. Such strategies are discussed in detail.
Stage IA to IIB mediastinal Hodgkin's disease: three-dimensional volumetric assessment of response to treatment.
Authors: Willett C G , Linggood R M , Leong J C , Miketic L M , Stracher M A , Skates S J , Kushner D C
Published: February 2017

From 1979 to 1986, the response to treatment of 53 patients with stage IA to IIB mediastinal Hodgkin's disease was evaluated by three-dimensional volumetric analysis using thoracic computed tomographic (CT) scans. The mean initial volume of mediastinal disease in 34 patients treated with mantle and para-aortic irradiation was 166 mL, whereas for 19 patients treated with two to six cycles of multiagent chemotherapy and mantle and para-aortic irradiation the mean initial volume was 446 mL. Preliminary data suggested that patients with mediastinal volumes of less than 200 mL had a lower mediastinal relapse rate (13%) than patients with volumes greater than 200 mL (32%). For 12 patients receiving six cycles of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), those with a greater than 85% reduction in volume 1 to 2 months after chemotherapy had a lower incidence of mediastinal relapse (zero of six, 0%) compared with patients having 85% or less reduction in volume (four of six, 67%). The primary value of this technique is that it provides a sensitive assessment of response to treatment and may aid in monitoring the effectiveness of a given treatment.
Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.
Authors: Miller R L , Bukowski R M , Budd G T , Purvis J , Weick J K , Shepard K , Midha K K , Ganapathi R
Published: February 2017

Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.
Extended mantle radiation therapy for pathologic stage I and II Hodgkin's disease.
Authors: Farah R , Ultmann J , Griem M , Golomb H , Kalokhe U , Desser R , Blough R , Weichselbaum R
Published: February 2017

Between 1968 and 1983, 135 patients with pathologic stage (PS) I and II Hodgkin's disease were treated with extended mantle radiation technique (EMRT) at Michael Reese Hospital and the University of Chicago Center for Radiation Therapy. EMRT combines both standard mantle and para-aorta fields (M-PA) in one port. Actuarial disease-free survival at 5 and 10 years was 82.5%. Actuarial overall survival was 96% and 83% at 5 and 10 years, respectively. Acute complications were evaluated in 112 patients available for analysis. Severe nausea and vomiting occurred in 13%, weight loss of greater than 10% of body weight in 19%, and acute hematologic toxicity in 4% of patients. Bone marrow suppression was transient and did not interfere with subsequent delivery of salvage treatment with either chemotherapy or radiation therapy in 22 patients who relapsed. The cost of EMRT is 40% lower than the cost of treatment with M-PA. The median treatment time was 38 days, 33% less than the 56 days for M-PA field assuming no interruptions. These results suggest that the EMT is a safe and effective treatment tolerated by most patients. The advantages of this method are eliminating the possibility of technical error of matching between mantle and para-aortic field, decreasing overall treatment time, and reducing the cost.
Methotrexate/fluorouracil scheduling influences normal tissue toxicity but not antitumor effects in patients with squamous cell head and neck cancer: results from a randomized trial.
Authors: Browman G P , Levine M N , Goodyear M D , Russell R , Archibald S D , Jackson B S , Young J E , Basrur V , Johanson C
Published: February 2017

To test the hypothesis that sequential scheduling of methotrexate (MTX) and fluorouracil (FU) produces a synergistic antitumor effect, we randomized 113 patients with recurrent or locally advanced squamous cell carcinoma of the head and neck to receive MTX-FU either 18 hours apart or simultaneously, with leucovorin rescue. There were 100 patients with locally advanced newly presenting disease and 13 patients with recurrence. Excessive toxicity was observed in the first 11 patients who received MTX 250 mg/m2 administered intravenously (IV) and leucovorin at 36 hours, therefore all subsequent patients received MTX 200 mg/m2 administered IV and leucovorin at 24 hours. FU 600 mg/m2 IV was administered to all patients, and treatment was given on days 1 and 8 of 21-day cycles. The treatment groups were well balanced for known prognostic variables. The response rate was 47.3% (26 of 55) for simultaneous v 44.8% (26 of 58) for sequential therapy. These results exclude a 20% difference in response rate favoring sequential therapy at P = .04. There was no observed difference in survival between the two treatment arms (P = .55) with a minimum follow-up of 8 months. Toxicity was greater in patients who received sequential therapy, and the difference was confined to the gastrointestinal (GI) tract. A comparison of the distribution in maximum Eastern Cooperative Oncology Group (ECOG) toxicity scores during chemotherapy for the two treatment groups showed greater stomatitis (P = .001), diarrhea (P = .04), and overall toxicity (P = .02) for sequential treatment without an observed difference in bone marrow toxicity. The results of this trial indicate that sequential MTX-FU is not superior to simultaneous therapy for the treatment of patients with head and neck cancer. Biochemical modulation of MTX-FU by drug scheduling may occur in vivo and may be organ specific.
A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors.
Authors: Bosl G J , Geller N L , Bajorin D , Leitner S P , Yagoda A , Golbey R B , Scher H , Vogelzang N J , Auman J , Carey R
Published: February 2017

Standard chemotherapy for disseminated germ cell tumors (GCT) cures most patients but causes considerable acute toxicity, including treatment-related death due to septicemia during neutropenia and pulmonary fibrosis. In addition, chronic and delayed toxicities, particularly Raynaud's phenomenon, have been reported in 6% to 37% of treated patients. In an attempt to minimize the acute and chronic effects of treatment which are related primarily to vinblastine and bleomycin, a randomized trial comparing the efficacy and toxicity of vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin (VAB-6) and etoposide + cisplatin (EP) was conducted on 164 eligible patients with good-prognosis GCT. Seventy-nine of 82 (96%) patients receiving VAB-6 and 76/82 (93%) receiving EP achieved a complete remission (CR) with or without adjunctive surgery. Similar proportions of patients in both arms were found at surgery to have necrosis/fibrosis or mature teratoma. With a median follow-up of 24.4 months in the VAB-6 arm and 25.9 months in the EP arm, the total, relapse-free, and event-free survival distributions were similar in the two arms. Patients receiving EP experienced less emesis (P = .05), higher nadir WBC (P = .06) and platelet counts (P = .01), less magnesium wasting (P = .0001), less mucositis (P = .09), and no pulmonary toxicity. No treatment-related mortality was observed. EP is an efficacious and less toxic regimen and is recommended for good-prognosis patients with disseminated GCT.