bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck.
Authors: Eisenberger M , Hornedo J , Silva H , Donehower R , Spaulding M , Van Echo D
Published: February 2017

Carboplatin (CBDCA, Bristol-Meyers, New York) is a second generation platinum analog. Preclinical and phase I clinical studies have indicated a different spectrum of toxicity compared with the parent compound. In order to study the activity of carboplatin against cancer of the head and neck, 31 patients with recurrent or metastatic disease (30 squamous-cell and one adenoid cystic carcinoma) were treated with doses of 60 to 80 mg/m2 administered daily by intravenous (IV) bolus injections for five days, repeated at every 4- to 5-week intervals. In most cases, treatment was administered on an outpatient basis. Eight patients (26%; 95% confidence interval, 12% to 45%) had complete (CR) or partial responses (PR) with a median duration of 4.5 months. Moderate bone marrow suppression was the main toxicity. Mild nausea and vomiting was unusual and no neuro- or nephrotoxicity were seen. These preliminary data suggest that carboplatin has activity against advanced squamous-cell carcinoma of the head and neck comparable with the results reported with cisplatin alone in similar patient populations. The potential advantages over the parent compound relate to the absence of nephrotoxic effects and mild gastrointestinal toxicity which allows for outpatient treatment. Because carboplatin toxicity is directly dependent on its mechanism of renal excretion, particular attention should be given for its use in patients with impaired renal function or when combined with nephrotoxic agents. Similarly, because the dose limiting toxicity with this agent is primarily hematologic, its use in combination with other myelotoxic agents should be carefully undertaken. Further studies are indicated in order to define the spectrum of activity of the new generation platinum analogs in various tumors in humans.
Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.
Authors: Chessells J M , Durrant J , Hardy R M , Richards S
Published: February 2017

The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival, intermittent continuing chemotherapy, although less immunosuppressive, is less effective than conventional continuous therapy in the treatment of ALL. In this study, 3 years of chemotherapy appeared superior to 2 years.
Anxiety and drug taste as predictors of anticipatory nausea in cancer chemotherapy.
Authors: Nerenz D R , Leventhal H , Easterling D V , Love R R
Published: February 2017

Interview data from 192 patients receiving cytotoxic chemotherapy for the first time were analyzed to identify factors predictive of the development of anticipatory nausea. Posttreatment nausea and vomiting (particularly vomiting), tastes of drugs during injections, and anxiety before injections were all associated with an increased probability of anticipatory nausea. An index consisting of those three variables, plus age, was found to have good predictive power, even when the predictor variables were assessed only at the first chemotherapy administration and the index was used to predict the development of anticipatory nausea at any time during the first six chemotherapy cycles.
Tumor heterogeneity and drug resistance.
Authors: Dexter D L , Leith J T
Published: February 2017

Drug resistance has long been identified as a major reason for therapy failure in cancer patients. Concurrently, work from many laboratories in the past 10 years has established tumor heterogeneity as a phenomenon of critical importance in the natural history of individual neoplasms. The two most sinister aspects of intraneoplastic diversity in human solid tumors are the genesis of clones with metastatic potential, and the existence of drug-resistant variants in primary cancers and their metastases. Thus, recent investigations on drug resistance and on tumor heterogeneity have converged to focus attention on the clonal organization of primary tumors and their metastases as the underlying basis for anticancer drug resistance. This review examines the degree of heterogeneity observed within tumors and the relationship of this diversity to resistance that might be anticipated for any given agent. A question critical to our discussion is "How many subpopulations are there?" The impact of multiple tumor clones on therapy is next discussed in relationship to normal tissue tolerance, the barrier clinicians face regardless of the specific agent used in treatment. Finally, laboratory and clinical approaches are presented for addressing a drug resistance problem that is seemingly overwhelming because of its complex biological roots.
Adjuvant adriamycin and cisplatin in newly diagnosed, nonmetastatic osteosarcoma of the extremity.
Authors: Ettinger L J , Douglass H O , Mindell E R , Sinks L F , Tebbi C K , Risseeuw D , Freeman A I
Published: February 2017

Twenty-two patients with newly diagnosed nonmetastatic osteosarcoma of the extremity were treated with an adjuvant chemotherapeutic regimen consisting of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin. Fourteen of the 22 patients remain continuously disease free for 65+ to 113+ months, with a median time on study of 70+ months. The 72-month disease-free survival estimate is 64%. Pulmonary metastases occurred in six patients, an isolated stump recurrence was seen in one patient, and one patient had a local recurrence following a limb-salvage procedure. For those patients in whom pulmonary metastases developed, the onset was late in three of six, and the number of metastases was three or fewer in all patients. Two patients with pulmonary metastases and one with a stump recurrence have apparently been salvaged, thus resulting in a 77% 72-month survival. Toxicity observed in patients treated with this regimen was in keeping with previous reports. This chemotherapeutic regimen is effective in the adjuvant therapy of nonmetastatic osteosarcoma of the extremity. It should be incorporated into other adjuvant protocols in an effort to continue to improve the outcome in patients with osteosarcoma.
Stage IIB Hodgkin's disease: the Stanford experience.
Authors: Crnkovich M J , Hoppe R T , Rosenberg S A
Published: February 2017

Between 1968 and 1982, 126 patients with pathologic stage (PS) IIB Hodgkin's disease were treated at Stanford University with either irradiation alone or irradiation combined with chemotherapy. Actuarial survival and freedom from relapse rates at 10 years for the overall group were 81% and 74% respectively, with no statistically significant difference between the treatment approaches. The impact of the severity and number of constitutional (B) symptoms, as defined by the Ann Arbor Conference, was analyzed. Patients who presented with all three B symptoms had significantly poorer survival and freedom from relapse compared with those patients with only one or two B symptoms (for survival differences, P = .005 and .007; for freedom from relapse differences, P = .002 and .04). Male sex was the only other prognostic factor that correlated with a poor outcome. At 10 years, the survival rate was 66% for males v 84% for females (P = .01), and the freedom from relapse rate was 75% for males v 89% for females (P = .02). The presence of extralymphatic sites of involvement, age greater than 40, or involvement of greater than three lymphoid sites had no significant adverse effect on either freedom from relapse or survival. Patients with large mediastinal masses treated with irradiation alone had a 10-year freedom from relapse rate of 54% v 81% for those treated with combined-modality therapy (P = .15), but there was no significant difference in survival rates (85% for irradiation alone v 71% for combined modality therapy). Treatment recommendations for stage IIB Hodgkin's disease are discussed.
Results of semen cryopreservation in young men with testicular carcinoma and lymphoma.
Authors: Reed E , Sanger W G , Armitage J O
Published: February 2017

Sixty-two young men with testicular carcinoma (31 patients) or lymphoma (31 patients) were referred for semen analysis and possible cryopreservation before systemic therapy. Seventy-seven percent of the patients, 24 patients with testicular carcinoma and 24 patients with lymphoma, had semen with a decreased chance for fertility (ie, sperm density less than 20 X 10(6)/mL and/or less than 40% motile sperm and/or decreased sperm motility). A decreased number of motile sperm as well as a poor grade of motility appeared in the majority of semen specimens from both patient groups. However, 14 patients had semen that met our criteria for fertility with sperm density greater than or equal 20 X 10(6)/mL, greater than or equal 40% motile sperm, and motility grade greater than 2. Semen quality appeared to be better in patients referred immediately after diagnosis than in patients in whom there was a delay between diagnosis and referral for semen cryopreservation. Twelve patients with semen meeting our criteria for possible fertility and 42 patients failing our criteria elected to cryopreserve semen. A median of three collections per patient were stored. To date, seven patients have withdrawn semen for artificial insemination by husband attempts, and two of these attempts have resulted in pregnancies. Both attempts involved patients with semen that meet our criteria for potential fertility. In the minority of young men with lymphoma or testicular carcinoma who have good-quality semen, semen cryopreservation can preserve reproductive potential after therapy that might otherwise cause sterility.
B cell acute lymphocytic leukemia in adults. Clinical, morphologic, and immunologic findings.
Authors: Gill P S , Meyer P R , Pavlova Z , Levine A M
Published: February 2017

Acute lymphocytic leukemia (ALL) is a heterogeneous group of disorders, clinically, immunologically, and pathologically. ALL of a B cell phenotype (B-ALL) is the least common. We have studied ten adult patients with B-ALL, none of whom had a tumor mass. The median age was 56 years (range, 30 to 90). A history of an altered immune state was noted in four cases: a distant history of Hashimoto's thyroiditis in one, pregnancy in one, and acquired immunodeficiency syndrome in two. Two patients presented with CNS involvement, and in two additional patients CNS leukemia developed during the course of disease. By the French-American-British (FAB) classification system, L3 leukemic morphology was present in nine, whereas L2 was present in one. Circulating leukemic blasts varied from less than 500/dL to greater than 15,000/dL. Eight patients were thrombocytopenic, and eight were anemic at presentation. Immunologic marker studies on leukemic blasts revealed monoclonal kappa light chain marking in nine and monoclonal lambda in one. Following chemotherapy, complete remission was achieved in three patients, two of whom experienced relapse within 9 months. The median survival for the group was 3 months, and only one patient experienced long-term, disease-free survival. We conclude that B-ALL in the adult presents with the classic L3 morphologic picture in the majority and is associated with extremely short survival.
Drug resistance in clinical practice: patterns of treatment failure in advanced breast and ovarian cancer.
Authors: Harnett P R , Kirsten F , Tattersall M H
Published: February 2017

We have analyzed the patterns of disease progression in patients with advanced breast and ovarian cancer receiving systemic therapy. Approximately 50% of patients developed progressive disease in a new, rather than a previously documented, disease site. Even when disease progressed in a previously involved disease site, in only half the cases was this identified as the bulk disease site before commencing treatment. The CNS was rarely a new site of disease progression in our patients, a finding that contrasts with a report that identified the CNS as the predominant new disease site in advanced breast cancer patients relapsing following a complete response. Progression of disease on second line treatment commonly occurred at sites of known disease. A number of factors influencing the pattern of disease progression have been examined. Disease progression on endocrine therapy tended to be more common in a previously involved disease site than in patients receiving cytotoxic therapy. There was a trend for patients who progressed within 6 months of chemotherapy to do so in an old site, whereas new disease sites predominated among those progressing later. Strategies for overcoming the causes of treatment failure should take account of the patterns of disease progression. Our results question the wisdom of always ceasing existing therapy when progressive disease is first documented.
Prognostic factors in stage I non-seminomatous germ-cell testicular tumors managed by orchiectomy and surveillance: implications for adjuvant chemotherapy.
Authors: Hoskin P , Dilly S , Easton D , Horwich A , Hendry W , Peckham M J
Published: February 2017

Between February 1979 and March 1985, 126 patients with clinical stage I non-seminomatous germ-cell testicular tumors were entered into a surveillance study after orchiectomy. Of this group, 36 (28%) have relapsed. The prognostic significance of 13 clinical, histopathologic, and biochemical factors has been analyzed. Vascular invasion and lymphatic invasion (LI) within the primary tumor, histology, and involvement of the epididymis and rete testis were significantly associated with an increased risk of relapse. However, multiple regression analysis showed that only histology and LI were significant, independent prognostic factors. These findings provide the basis for the consideration of adjuvant chemotherapy for patients with apparent clinical stage I testicular non-seminoma who are at high risk of harboring occult metastases.
Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer.
Authors: Einhorn L H , Loehrer P J , Williams S D , Meyers S , Gabrys T , Nattan S R , Woodburn R , Drasga R , Songer J , Fisher W
Published: February 2017

In this phase III randomized study, 124 evaluable patients with unresectable non-small-cell lung cancer (NSCLC) were randomized to vindesine v cisplatin (120 mg/m2) plus vindesine v cisplatin (60 mg/m2) plus vindesine plus mitomycin C. The objective response rate for cisplatin and vindesine was 27% v 20% for cisplatin, vindesine, and mitomycin C, and 14% for vindesine alone (P = .25 for cisplatin and vindesine v vindesine). The percentage of patients having stable disease (no progression for a minimum of 3 months) was 20% (cisplatin and vindesine), 27% (cisplatin, vindesine, and mitomycin C), and 26% (vindesine alone), respectively. The median survival time for vindesine was 18 weeks, compared with 26 weeks for cisplatin and vindesine and 17 weeks for cisplatin, vindesine, and mitomycin C. Overall survival was not statistically different for cisplatin plus vindesine v vindesine (P = .65). There was no evidence for improved duration of remission or survival of responders with the cisplatin (120 mg/m2) and vindesine arm. This study failed to demonstrate sufficient therapeutic benefit for cisplatin and vindesine (+/- mitomycin C) compared with single-agent vindesine to justify the increased cost and toxicity of these combination regimens.
A phase II study of combined 5-fluorouracil, doxorubicin, and cisplatin in the treatment of advanced upper gastrointestinal adenocarcinomas.
Authors: Moertel C G , Rubin J , O'Connell M J , Schutt A J , Wieand H S
Published: February 2017

In a phase II study of 67 patients with upper gastrointestinal carcinomas and measurable disease without previous chemotherapy, we have evaluated the combination of intensive course 5-fluorouracil (5-FU) (300 mg/m2/d for five days) doxorubicin (40 mg/m2 on day 1), and cisplatin (60 mg/m2 on day 1). Courses were repeated every 5 weeks. Among 26 patients with gastric carcinoma, a 50% regression rate was obtained with a median survival for all patients of 9 months. Among 29 patients with pancreatic carcinoma, the regression rate was 21% and the median survival was 4 months. Regressions were also observed in smaller numbers of patients with carcinomas of the gallbladder and ampulla of Vater, as well as in cholangiocellular carcinoma of the liver. Toxic reactions were usually clinically tolerable and consisted primarily of nausea, vomiting, stomatitis, diarrhea, leukopenia, and alopecia. Phase III studies are in progress to place the value of this experimental regimen into clinical perspective.
Phase I study of multiple dose intramuscularly administered recombinant gamma interferon.
Authors: Kurzrock R , Quesada J R , Talpaz M , Hersh E M , Reuben J M , Sherwin S A , Gutterman J U
Published: February 2017

We report the results of a phase I study of the tolerance and biologic activity of intramuscularly (IM)-administered recombinant interferon-gamma (rIFN-gamma). Forty-four patients with metastatic cancer were given rIFN-gamma at doses ranging from 0.01 to 2.5 mg/m2/d for 42 days. The most common side effects were fever, flulike symptoms, night sweats, and granulocytopenia. The maximum tolerated dose was 0.5 mg/m2/d. Administration of rIFN-gamma resulted in modulation of immune system functions, including induction of major histocompatibility complex-associated antigens on blood leukocytes, an increase in blood surface immunoglobulin-bearing B cell and natural killer (NK) cell number, and NK cell cytotoxicity. Serum lysozyme, determined as an estimate of tissue macrophage activity, also increased. Serum assays for anti-interferon antibodies were negative in all patients. Five of eight evaluable patients with lymphoproliferative disorders showed objective evidence of tumor regression consisting of partial responses (two patients), and minor responses (three patients). These data suggest that further phase II studies of IM-administered rIFN-gamma are indicated.
Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate.
Authors: Body J J , Borkowski A , Cleeren A , Bijvoet O L
Published: February 2017

Treatment of malignancy-associated hypercalcemia remains unsatisfactory. We have prospectively treated 26 consecutive hypercalcemic cancer patients with intravenous (IV) aminohydroxypropylidene diphosphonate (APD). The drug was administered daily as a 15-mg two-hour IV infusion until both serum and urinary calcium had been normalized for 48 hours. Twenty-four patients were fully evaluable (eight head and neck tumors, seven breast cancers, three epidermoid tumors of the lung, and six miscellaneous neoplasms). Whereas rehydration had only inconsistent effects, APD normalized serum calcium in all patients after a mean of three daily doses: serum calcium decreased from 13.3 +/- 0.4 mg/dL (mean +/- SEM) before APD to 8.0 +/- 0.1 mg/dL at the end of treatment. Ionized calcium declined in parallel to total calcium. APD was as effective in hypercalcemia due to bone metastases as in paraneoplastic hypercalcemia. The drug was tolerated without toxicity and had a prolonged effect: serum calcium remained normal during 3+ weeks (1 + to 8 +) in 17 patients who did not receive or did not respond to antitumoral treatment. APD normalized serum calcium by inhibiting bone resorption, as evidenced by the dramatic decrease in urinary excretion of calcium and hydroxyproline. Inhibition of bone resorption was probably also responsible for the decrease in serum phosphorus from 2.9 +/- 0.2 to 2.0 +/- 0.1 mg/dL. In summary, IV APD constitutes a major advance in the treatment of malignancy-associated hypercalcemia: it is very effective, well tolerated, and has a prolonged efficacy.
Twenty years of MOPP therapy for Hodgkin's disease.
Authors: Longo D L , Young R C , Wesley M , Hubbard S M , Duffey P L , Jaffe E S , DeVita V T
Published: February 2017

The results of treatment of 198 patients with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) for Hodgkin's disease were analyzed after a median of 14 years of follow-up. Throughout the period of follow-up, 103 patients have remained continuously free of disease. Review of biopsy specimens of 43 patients originally classified as Hodgkin's disease, lymphocyte-depleted type, revealed that ten of these patients actually had diffuse immunoblastic or large cell non-Hodgkin's lymphomas. Of the 188 patients with Hodgkin's disease, 157 achieved a complete response (CR) (84%), and 66% of them (101 patients) have remained disease-free more than 10 years from the end of treatment. Absence of B symptoms and receiving higher doses of vincristine were factors associated with a higher CR rate and longer survival. Patients entering complete remission in five cycles or less had significantly longer remissions than those requiring six or more cycles. Forty-eight percent of the Hodgkin's disease patients have survived between 9 and 21 years (median, 14 years) from the end of treatment. Nineteen percent of the CRs have died of intercurrent illnesses, free of Hodgkin's disease.
Importance of primary site in assessing chemotherapy response and 7-year survival data in advanced squamous-cell carcinomas of the head and neck treated with initial combination chemotherapy without cisplatin.
Authors: Hill B T , Price L A , MacRae K
Published: February 2017

Two hundred eight patients with advanced head and neck squamous-cell carcinomas were treated between 1975 and 1982 with schedule A chemotherapy containing vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours followed by a folinic acid rescue. Chemotherapy was administered as initial treatment on days 1 and 14 before "curative" local therapy. Toxicity was minimal and patient compliance was 100%. Chemotherapy response was assessed on day 28 in 200 patients: 132 (66%) had an objective response and 68 (34%) were judged to be nonresponders. The complete remission (CR) rate following local therapy was significantly greater in chemotherapy responders (78%) than nonresponders (49%) (P less than .001). Overall median survival figures were 32 months for all patients, 37 months for all chemotherapy responders, and 69 months for all patients achieving CR. Analysis by tumor site showed that oral cavity or nasopharyngeal tumors responded well to initial chemotherapy (P less than .05 and P less than .01) compared with all other sites. This high response rate was not necessarily associated with increased survival, since the median survival of chemotherapy responders for oral cavity lesions was only 22 months, although in nasopharyngeal tumors, median survival figures were 64 months. Furthermore, the longest median survival duration of 69 months was observed in patients with laryngeal tumors, although these had a lower response rate (61%) to initial chemotherapy. Therefore, response to initial chemotherapy is not automatically a favorable prognostic sign. Survival figures appear markedly influenced by tumor site.
Photodynamic therapy for palliation of locally recurrent breast carcinoma.
Authors: Schuh M , Nseyo U O , Potter W R , Dao T L , Dougherty T J
Published: February 2017

Fourteen women with locally recurrent breast carcinoma on the chest wall following mastectomy were given 30 courses of photodynamic therapy (PDT). All patients had been heavily pretreated with conventional modes of therapy (radiation therapy, chemotherapy, hormonal therapy, surgical resection). Twenty-two courses yielded a partial response; two courses yielded a complete response; four courses showed no response; one patient was treated as an adjunct to surgery; and one patient was lost to follow-up. Duration to response was variable, ranging from 6 weeks to 8 months. Several women had chest wall disease controlled for prolonged periods of time using repeated courses of PDT. Two women had re-epithelialization of ulcerated lesions. Complications were minimal and included pain (two patients), sunburn (two), and infection (one). These results suggest that treatment with PDT can aid in local control of chest wall recurrence following mastectomy in selected patients.
Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study.
Authors: Alberts D S , Kronmal R , Baker L H , Stock-Novack D L , Surwit E A , Boutselis J G , Hannigan E V
Published: February 2017

Cisplatin has proven to be the most active single agent in the treatment of metastatic and recurrent squamous cell cancer of the cervix. In a previous southwest Oncology Group (SWOG) pilot study, the addition of cisplatin to a mitomycin-C, vincristine, and bleomycin (MVB) regimen resulted in a relatively high percentage of durable complete responses. To gain more experience with cisplatin-based chemotherapy regimens, the SWOG initiated a phase II randomized trial of cisplatin, mitomycin-C plus cisplatin (MC), and MVB plus cisplatin (MVBC) in 119 patients with advanced squamous cell cancer of the cervix and no prior chemotherapy exposure. Because of slow patient accrual early in the trial, the cisplatin arm was discontinued. Five patients were declared ineligible according to protocol criteria. The three treatment groups were relatively well matched for age, prior radiation exposure, and sites of measurable disease. The overall objective response rates for cisplatin, MC, and MVBC treated patients were 33%, 25%, and 22%, respectively. Median response durations were greater than 6 months. Median survival durations associated with cisplatin, MC, and MVBC treatment were 17.0, 7.0, and 6.9 months, respectively. There were no drug-related deaths. Severe or life-threatening leukopenia and thrombocytopenia were observed in 18% to 24% of patients treated with MVBC and MC, but in none of those receiving cisplatin alone. We conclude that the low response rates and short durations of both response and survival observed in patients randomized to the two chemotherapy combinations suggest that only enhanced toxicity was gained through the addition of mitomycin-C or MVB to cisplatin in patients with advanced cervix cancer.
Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes.
Authors: O'Donnell M R , Nademanee A P , Snyder D S , Schmidt G M , Parker P M , Bierman P J , Fahey J L , Stein A S , Krance R A , Stock A D
Published: February 2017

Twenty patients (age range, 4 to 48 years; median age, 36 years) with de novo or drug-induced myelodysplastic syndromes or myeloproliferative disorders were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Four preparative regimens were used; three regimens consisted of combined total body irradiation (TBI) and chemotherapy and one of combination chemotherapy only. One patient received marrow from his identical twin brother, whereas the other 19 patients were grafted with marrow from histocompatible siblings. In 19 patients the abnormal clone was at least temporarily ablated, while in one patient the congenital myelodysplasia persisted. Eight patients are alive and well for +108 to +3,359 days post-transplantation. Nine patients died of transplant-related complications (six of interstitial pneumonia, two of gastrointestinal bleeding, and one of fungal sepsis) and three patients died with persisting or recurring disease. One patient with a late recurrence has undergone a second successful bone marrow transplant procedure. Outcome of BMT was not related to French-American-British (FAB) type, marrow fibrosis, cytogenetic abnormalities, or preparation regimen. Marrow transplantation as a means of providing long-term disease-free survival and possible cure should be considered in patients if a suitable donor is available.
Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study.
Authors: Humblet Y , Symann M , Bosly A , Delaunois L , Francis C , Machiels J , Beauduin M , Doyen C , Weynants P , Longueville J
Published: February 2017

A multicentric randomized prospective trial was conducted to test whether late intensification chemotherapy would increase the remission rate, the relapse-free survival, and the survival of small-cell lung cancer patients responding to induction chemotherapy. Autologous bone marrow transplantation was used as support to reduce the duration of the aplasia induced by very high-dose chemotherapy. As induction chemotherapy, 101 patients received, during a period of 5 months, a total dosage of 120 mg/m2 methotrexate, 4.5 mg/m2 vincristine, 1,800 mg/m2 cyclophosphamide, 180 mg/m2 doxorubicin, 160 mg/m2 cisplatin, 750 mg/m2 VP-16-213, and 30 Gy prophylactic cranial irradiation. Forty-five patients, selected for their sensitivity to this induction treatment, were randomized to a last cycle of chemotherapy that combined cyclophosphamide, BCNU, and VP-16-213 either at a conventional dosage of 750 mg/m2 intravenously (IV), 60 mg/m2 IV, and 600 mg/m2 orally or alternatively at a very high dosage of 6 g/m2 IV, 300 mg/m2 IV, and 500 mg/m2 IV, respectively. In the late intensification group, the complete remission rate increased from 39% before randomization to 79% after high-dose chemotherapy. Median relapse-free survivals after randomization for intensified and control chemotherapy groups were 28 and 10 weeks, respectively (P = .002). Median overall survival after induction therapy was 68 weeks for the intensified group compared with 55 weeks for the conventional therapy group (P = .13). Four patients died during intensification. Patients in both groups relapsed at the primary site. It can thus be concluded that late intensification chemotherapy for sensitive small-cell lung cancer increases the complete remission rate and resulted in a statistically significant increase in the relapse-free survival. However, since relapse occurred at the primary site and toxicity was high, overall survival was not significantly improved.
High-dose induction chemotherapy of metastatic breast cancer in protected environment: a prospective randomized study.
Authors: Hortobagyi G N , Buzdar A U , Bodey G P , Kau S , Rodriguez V , Legha S S , Yap H Y , Blumenschein G R
Published: February 2017

To test the hypothesis of whether high doses of chemotherapy in combination achieve higher response rates and longer durations of response and survival, we treated 33 pre- and perimenopausal patients with good performance status in a prospective trial with escalating doses of fluorouracil, doxorubicin and cyclophosphamide (FAC). Patients were randomly assigned to be treated within a protected environment (laminar air flow room), with prophylactic antibiotics, or in a standard hospital room. Important patient characteristics were equally distributed in the two treatment arms. A major objective response was observed in 27 of the 32 evaluable patients (84%), and 11 (34%) achieved a complete remission (CR). There was no significant difference in overall and complete response rates between the two treatment arms, nor was there a substantial difference in times to progression or survival between the groups treated in or out of the protected environment. Comparison of the results of this study with previously reported programs of FAC chemotherapy in patients with metastatic breast cancer shows that this study achieved higher overall and complete response rates. However, neither the time to progression, nor the survival of responders or the entire patient group was different from our previous experience with standard FAC chemotherapy. When the study was initiated in 1976, the proposed dose escalation represented high-dose chemotherapy. In retrospect, even the "high" doses used in this study represent only a modest increase over standard doses of chemotherapy. Much steeper dose escalations will be needed to evaluate the efficacy of high-dose chemotherapy in breast cancer, as well as the protective value of the protected environment and prophylactic antibiotics in metastatic breast cancer.
Retroperitoneal fibrosis following treatment for Hodgkin's disease.
Authors: Chao N , Levine J , Horning S J
Published: February 2017

With improvement and refinement of therapy, the majority of Hodgkin's disease patients are alive and free of disease at 5 years. As these patients continue to be observed, a variety of late complications have been reported. We describe herein three patients who developed retroperitoneal fibrosis following definitive therapy for Hodgkin's disease. The incidence approaches that seen with methysergide.
Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer.
Authors: Levy S , Herberman R , Lippman M , d'Angelo T
Published: February 2017

Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.
Nonoperative therapy for squamous-cell cancer of the esophagus.
Authors: Leichman L , Herskovic A , Leichman C G , Lattin P B , Steiger Z , Tapazoglou E , Rosenberg J C , Arbulu A , Asfaw I , Kinzie J
Published: February 2017

Based on the surgical pathology and survival for patients in previous trials using a neoadjuvant program of chemotherapy (5-fluorouracil [5-FU]-cisplatin) and radiation (3,000 cGy) before surgery for squamous-cell cancer (SCC) of the esophagus, a nonoperative pilot trial was designed to test if survival and recurrence would differ from our historical controls if routine esophagectomy was eliminated. Twenty patients were treated. The protocol called for the delivery of 5-FU infusion (1,000 mg/m2/d X 4 d) days 1 to 4 and 29 to 32 with cisplatin (100 mg/m2) day 1 and 29 sandwiched around external beam radiation (3,000 cGy over 3 weeks). Mitomycin C (10 mg/m2) day 57 was administered with bleomycin infusion (20 U/d X 4 d) days 57 to 60 and 78 to 81. A radiation boost of 2,000 cGy was administered 200 cGy/d days 99 to 103 and 106 to 110. Clinical pulmonary toxicity forced withdrawal of bleomycin and mitomycin C in the last four patients treated; two further courses of 5-FU-cisplatin were administered instead. The median measurement of the 20 esophageal lesions by barium swallow was 7 cm. Four patients underwent salvage surgery to prevent life-threatening aspiration pneumonia. The median survival for the 20 patients is 22 months, with a range from 6 to 39+ months. The six patients clinically without cancer are alive 22+ to 39+ months (median, 35+ months). Three patients died manifesting only local (infield) recurrence; five died manifesting only distant recurrence; and five developed local and distant recurrence. While the toxicity of the four drug regimen as administered was prohibitive, the survival and quality of survival is superior to the regimen previously used, which routinely used surgery after preoperative chemotherapy and radiation.
High-dose intensity systemic therapy of metastatic bladder cancer.
Authors: Hrushesky W J , Roemeling R V , Wood P A , Langevin T R , Lange P , Farley E
Published: February 2017

Forty-three consecutively diagnosed patients with widely metastatic transitional cell carcinoma of the bladder (TCCB) were treated with a high-dose intensity, chronobiologically timed combination of doxorubicin and cisplatin, followed by Cytoxan (Mead Johnson Pharmaceuticals, Evansville, IN), 5-fluorouracil (5-FU), and cisplatin maintenance for up to 2 years. Fifty-seven percent of the 35 evaluable patients with widespread metastatic cancer responded objectively. Twenty-three percent had complete disappearance of all cancer. Median survival from first treatment for complete responders (CRs) was more than 2 years, and 1 year for partial responders (PRs). Three of the CRs were alive without evidence of cancer more than 2 years after stopping all therapy. High-dose intensity combination chemotherapy can induce durable CRs of widespread bladder cancer.
Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).
Authors: Baker L H , Frank J , Fine G , Balcerzak S P , Stephens R L , Stuckey W J , Rivkin S , Saiki J , Ward J H
Published: February 2017

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.
Evaluation of intensive postremission chemotherapy for adults with acute nonlymphocytic leukemia using high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide.
Authors: Tallman M S , Appelbaum F R , Amos D , Goldberg R S , Livingston R B , Mortimer J , Weiden P L , Thomas E D
Published: February 2017

In order to test the toxicity and efficacy of intensive postremission therapy with high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide in adults with acute nonlymphocytic leukemia (ANL), 100 adults (ages 19 to 75) with previously untreated ANL were entered into a study using six sequential cycles of chemotherapy. Cycles 1 (induction), 3, and 5 included conventional doses of daunomycin, cytosine arabinoside, 6-thioguanine, vincristine (VCR), and prednisone. Cycle 2 was cytosine arabinoside 3 g/m2 intravenously (IV) every 12 hours for four doses, followed by L-asparaginase 10,000 U intramuscularly (IM) at hour 42; this combination was repeated 1 week later. Cycle 4 included amsacrine 120 mg/m2/d and etoposide 100 mg/m2/d, both IV for five days, and cycle 6 was three monthly courses of VCR on day 1, and prednisone, mercaptopurine, and methotrexate each for five days. Seventy-four patients (74%) achieved complete remission (CR) (51 with cycle 1 and 23 after cycle 2). The overall disease-free survival (DFS) for patients achieving CR is 27% at 3 years by Kaplan-Meier analysis, while for patients achieving CR with cycle 1 it is 34%. The actuarial probability of being free from relapse at 3 years for patients achieving CR is 34%. Sixteen of the 74 CR patients (22%) died in CR while continuing to receive intensive chemotherapy, including 12 (18%) who succumbed to infection (nine bacterial, three fungal). After a median follow-up of 20 months, 36 patients have relapsed and 21 remain alive in CR. Intensive consolidation with high-dose cytosine arabinoside, amsacrine, and etoposide can modestly prolong DFS compared with historical controls. However, relapse continued to be a major problem and, in addition, with more aggressive consolidation therapy, infection during marrow aplasia resulted in a significant number of deaths.
Subdiaphragmatic Hodgkin's disease: laparotomy and treatment results in 49 patients.
Authors: Leibenhaut M H , Hoppe R T , Varghese A , Rosenberg S A
Published: February 2017

The clinical records of 1,616 patients with previously untreated Hodgkin's disease were reviewed. Forty-nine of these patients (3%) presented with disease limited to sites below the diaphragm and underwent laparotomy as part of their staging evaluation. The clinical and histological characteristics of this group of patients with subdiaphragmatic Hodgkin's disease are compared with those who presented with supradiaphragmatic disease. Splenectomy in 47 patients revealed splenic involvement in 16 (39%), and bulky splenic involvement (more than five gross nodules) in ten (24%). The final pathological stage (PS) distribution was PS I = 8, PS II = 37, PS IV = 4. No clinical stage (CS) IA patients and only two of 20 patients with negative paraaortic nodes on lymphogram had splenic involvement in contrast to eight of nine CS IIB patients. Freedom from relapse and survival were similar to patients with equivalent stage supradiaphragmatic disease. Splenic involvement and bulky splenic involvement were associated with a significantly decreased survival. Twelve out of 44 PS IA to IIB patients relapsed. In eight of these 12 patients, relapse was limited to sites above the diaphragm and another two patients relapsed both above and below the diaphragm. Patients who received total lymphoid irradiation were less likely to relapse above the diaphragm than patients who received no supradiaphragmatic irradiation. We recommend that CS IA and IIA patients with subdiaphragmatic disease undergo staging laparotomy and receive supradiaphragmatic irradiation as part of their treatment. Laparotomy may not be necessary for CS IIB patients who are at high risk for splenic disease if chemotherapy is planned as part of their treatment program.