bluuebunny/crossref_metadata_2025 huggingface dataset:
The treatment of advanced metastatic seminoma: experience in 55 cases.
Authors: Fosså S D , Borge L , Aass N , Johannessen N B , Stenwig A E , Kaalhus O
Published: February 2017

Thirty-six of 39 previously untreated evaluable patients with advanced metastatic seminoma (stage greater than or equal to IIb) obtained a complete response (CR) and three a partial response (PR) after cisplatin-based combination chemotherapy with or without surgery/radiotherapy (group 1). After a median observation time of 36 months, 33 patients are alive with no evidence of disease (NED). Fifteen additional patients received cisplatin-based chemotherapy due to relapsing seminoma after initial radiotherapy (group 2). Thirteen patients obtained a CR, and two a PR. Patients from group 1 lived significantly longer after the start of chemotherapy than those from group 2. The rate and severity of the treatment-related complications were comparable in both groups. The most frequent nonfatal side effects of cisplatin-based combination chemotherapy were Raynaud-like phenomena, polyneuropathy, and myelosuppression. Four patients developed fatal complications (septicemia, bone marrow aplasia). In three of 12 patients with evaluable postchemotherapy histology, vital malignant seminoma was found. Cisplatin-based combination chemotherapy in advanced seminoma patients is highly effective, but includes a significant risk of severe complications. Less toxic treatment regimens should be explored, at least for patients who have less advanced tumors (stage IIb/limited stage IIc).
Phase II study of interferon alfa-2a, recombinant (Roferon-A) in metastatic renal cell carcinoma.
Authors: Buzaid A C , Robertone A , Kisala C , Salmon S E
Published: February 2017

In an attempt to decrease toxicity without compromising efficacy, 22 patients with locally advanced or metastatic renal cell carcinoma (RCC) were treated with recombinant interferon alfa-2a (rIFN alpha 2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) intramuscularly (IM) beginning at a dose of 3 X 10(6) U/d with incremental dose escalations to the highest dose of 36 X 10(6) U/d if tolerated, for a total induction period of 10 weeks. Patients demonstrating complete (CR), partial (PR), or minor (MR) responses or stabilization were continued on a maintenance regimen of the highest tolerated dose administered three times weekly until disease progression. Doses administered during maintenance were individually determined as the maximum dose that resulted in only mild toxicity. No CRs were achieved. Partial responses were observed in 23% of the patients with a median duration of response of 8.0 months (range, 1 to 17+). The majority of interferon side effects were seen during the induction phase, which was also the period requiring the most frequent adjustments in dose. In comparison to another study using similar toxicity criteria, overall toxicity was reduced in severity, most probably due to the study design, which allowed individual tailoring of doses. The use of an initial induction phase employing rapid dose escalation followed by a well-tolerated maintenance phase appeared to be a reasonable strategy. The therapeutic results to date represent a modest advance. An optimal dosage, route, and schedule for interferon administration for metastatic renal cancer is not yet clearly established.
Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease.
Authors: Cline M J , Battifora H , Yokota J
Published: February 2017

DNAs from fifty-three primary breast cancers were hybridized with 16 different proto-oncogene or oncogene probes. Abnormalities of one or more of five proto-oncogenes were found in fifty-eight percent of tumors at the time of mastectomy. Amplification of c-myc and c-erbB-2, and allelic deletions of c-ras-Ha and c-myb were the most common abnormalities. The presence of altered proto-oncogenes correlated with clinical stage of the cancers. Fifteen of 43 evaluable tumors of stages I to III recurred, and four of five evaluable stage IV tumors progressed within 16 to 24 months of surgery. All but one of the cancers that recurred or progressed had detectably altered proto-oncogenes (P less than .001). Analysis of proto-oncogenes may have prognostic value in breast cancer.
Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy.
Authors: Hainsworth J D , Wright E P , Gray G F , Greco F A
Published: February 2017

We have previously reported complete responses and long-term survival in patients with metastatic poorly differentiated carcinoma (PDC) of unknown primary site who received intensive cisplatin-containing chemotherapy regimens. We reviewed the light microscopic specimens from 113 patients with PDC in an attempt to identify common histopathologic features in the chemotherapy-responsive subgroup, and to rule out the presence of previously unrecognized germ cell tumors. Relatively few diagnoses more specific than PDC could be made. We could identify no histopathologic features by light microscopy that distinguished responsive from unresponsive neoplasms. Only one patient was found to have a previously unrecognized yolk sac carcinoma, and in five other patients the possibility of a germ cell neoplasm was considered in the differential diagnosis by at least one reviewer. The remaining tumors had no histologic features suggestive of germ cell neoplasms. Ninety-six patients had received combination chemotherapy (89 with cisplatin-containing regimens); 27 patients (28%) achieved complete remission, and 16 remain free of disease at a median of 65 months after completion of therapy. Patients with PDC of unknown primary site who are responsive to cisplatin-containing chemotherapy regimens cannot be reliably identified by light microscopy. At present, all such patients should be considered for an empiric trial of chemotherapy with cisplatin-based regimens, since cure is achievable in a minority.
Spontaneous fracture of the catheter of a totally implantable venous access port: case report of a rare complication.
Authors: Noyen J , Hoorntje J , de Langen Z , Leemslag J W , Sleijfer D
Published: February 2017

A case of spontaneous fracture of the outlet catheter of a totally implantable venous access port (IVAP) is presented. Thirty-seven weeks after implantation, the outlet catheter was broken at the entrance into the left subclavian vein. The distal part was embolized in the left pulmonary artery. The embolized remnant was retrieved in an outpatient setting, using a grasping forcipal catheter through a 7 French longsheath. Experimental study of the catheter revealed that it had been broken due to a local cause, probably the long-standing compression at the narrow space between clavicle and first rib. It is emphasized to ascertain the position and intactness of an IVAP before using it to infuse cytostatic agents.
Clinical usefulness of an algorithm for the early diagnosis of spinal metastatic disease.
Authors: Redmond J , Friedl K E , Cornett P , Stone M , O'Rourke T , George C B
Published: February 2017

We have previously reported an algorithm that invokes several imaging modalities in the early detection of metastatic and benign disease of the spine in patients with cancer (J Clin Oncol 4:576, 1986). The development of new lesions (shown by Tc99m bone scans) in cancer patients with normal neurological examinations is further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M). Of 60 patients in the original study, 28% were diagnosed as having only benign disease and the remainder had spinal metastases. Thecal sac impingement was seen in 47% of patients with metastatic disease and disruption of the posterior vertebral cortex was noted in all patients with epidural compression. We now report the 2-year follow-up of 55 of these patients. Without treatment, the 17 patients diagnosed with benign disease have shown no evidence of local failure in the spine and median survival is greater than 27 months. Thirty-eight patients diagnosed with spinal metastases had a median survival time of 16.9 months. Radiation therapy directed by CT-M findings provided pain relief in 78% of patients with back pain and metastatic disease. No patient, including 19 with thecal sac impingement, developed clinical myelopathy. These results demonstrate the usefulness of an imaging algorithm for the early identification and distinction of spinal metastatic disease and benign disease in patients with cancer.
A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer.
Authors: Eagan R T , Frytak S , Richardson R L , Creagan E T , Therneau T M , Coles D T , Jett J R
Published: February 2017

One hundred eight eligible patients with advanced, metastatic non-small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, and cisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non-cross resistance.
Correlation of karyotype and immunophenotype in childhood acute lymphoblastic leukemia.
Authors: Pui C H , Williams D L , Roberson P K , Raimondi S C , Behm F G , Lewis S H , Rivera G K , Kalwinsky D K , Abromowitch M , Crist W M
Published: February 2017

To correlate leukemic cell karyotype with immunophenotype, we studied 364 children with acute lymphoblastic leukemia (ALL). A prognostically favorable cytogenetic feature, hyperdiploidy greater than 50 chromosomes, was found in 33% of cases classified as common ALL antigen positive (CALLA+) early pre-B (common) ALL, in contrast to 18% of pre-B cases (P = .012), 5% of T cell cases (P less than .001), and none of the B cell cases (P less than .001) or cases of CALLA negative (CALLA-) early pre-B ALL (P = .002). The frequency of translocations, an adverse cytogenetic feature, was significantly lower in CALLA+ early pre-B ALL cases (35%) than in B cell (100%; P less than .0001), pre-B (59%; P less than .001), or CALLA- early pre-B (62%; P = .016) cases. Thus, patterns of chromosomal change differ widely among the major immunophenotypic groups of ALL and may account for reported differences in responsiveness to treatment.
Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologic correlation.
Authors: Newton W A , Soule E H , Hamoudi A B , Reiman H M , Shimada H , Beltangady M , Maurer H
Published: February 2017

Histopathologic material from 1,782 patients registered in the Intergroup Rhabdomyosarcoma Study Committee (IRS)-I and -II were reviewed by the IRS Pathology Committee in order to provide a uniform approach to classification and correlate patient survival with tumor type. Categories considered eligible were the four types of rhabdomyosarcoma (RMS) (criteria of Horn and Enterline), extraosseous Ewing's tumor (EOE), and a group of somewhat variable undifferentiated sarcomas designated small round cell sarcoma, type indeterminate (STI). Tumors that were clearly sarcomas but were unclassifiable also were included (NOS). The committee diagnoses were embryonal (Emb) RMS in 877 (54%), alveolar (Alv) RMS in 343 (21%), botryoid (Botr) RMS in 88 (5%), pleomorphic (Pleo) RMS in 11 (1%), STI in 135 (8%), and EOE in 84 (5%). One in nine were mixtures of types, eg, Emb and Alv. Five percent of the sarcomas could not be classified because of inadequate material. In general, there was close agreement (94%) between the review committee and institutional pathologists in the diagnosis of RMS, but not in the specific types, particularly Alv RMS (41%) and STI (36%). This observation is important, since patients with Alv RMS and STI tumors had decreased survival compared with the other histologies. The prognosis varied by histology, with Botr having the best, Alv RMS and STI the worst, and Emb RMS and EOE an intermediate prognosis.
A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission.
Authors: Zander A R , Keating M , Dicke K , Dixon D , Pierce S , Jagannath S , Peters L , Horwitz L , Cockerill K , Spitzer G
Published: February 2017

From July 1980 to November 1985, 109 patients with acute myelogenous and lymphoblastic leukemia who had reached a complete remission (CR) following induction treatment were assigned to a study comparing marrow transplantation with chemotherapy as a postremission treatment. Sixty-nine patients did not have a human leukocyte antigen (HLA)-identical donor, and therefore served as chemotherapy controls; 40 patients had HLA-identical donors, and therefore were assigned to the transplant arm. Of these, 23 were transplanted in first remission and 17 were not. Ten of these 17 were subsequently transplanted in relapse. Initially, only patients with poor prognosis determined by a predictive model were entered into the study. Subsequently, patients with moderately poor prognosis were admitted. Comparing the chemotherapy group with the patients transplanted in first CR, significant control of leukemia relapse in transplanted patients was seen in the subgroup with acute myelogenous leukemia (AML) (P less than .1), and acute lymphoblastic leukemia (ALL) (P less than .01), in the poor (P = .01) and intermediate subgroup (P = .01), and in the good-prognostic groups (P = .05). The survival was affected significantly in only the poor and intermediate subgroups. The use of predictive models might help to select patients for whom bone marrow transplantation is appropriate in first remission and those for whom bone marrow transplantation can be left as the initial treatment of relapse. Predictive models could further be helpful in comparing studies performed at different transplant centers.
Successful marrow transplantation for acute myelocytic leukemia following therapy for Hodgkin's disease.
Authors: Geller R B , Vogelsang G B , Wingard J R , Yeager A M , Burns W H , Santos G W , Saral R
Published: February 2017

Five patients with acute myelocytic leukemia (AML) after combined modality therapy for Hodgkin's disease (HD) were treated with cyclophosphamide and busulfan followed by bone marrow transplantation (BMT). Four patients received allogeneic transplants from histocompatibility locus antigen (HLA)-compatible siblings and the fifth patient received an autologous marrow treated with 4-hydroperoxycyclophosphamide. Two patients died of complications of acute graft-v-host disease (GVHD) despite prophylaxis with either low-dose cyclophosphamide or cyclosporine. The remaining three patients were alive and disease-free 382, 617, and 620 days after transplant. These initial results are encouraging and more patients with treatment-related AML need to be evaluated with both allogeneic and autologous BMT to fully elucidate the potentially curative role of this intensive therapy in an otherwise fatal hematologic malignancy.
Surgically documented response to intraperitoneal cisplatin, cytarabine, and bleomycin after intravenous cisplatin-based chemotherapy in advanced ovarian adenocarcinoma.
Authors: Piver M S , Lele S B , Marchetti D L , Baker T R , Emrich L J , Hartman A B
Published: February 2017

Thirty-one evaluable patients with stages III and IV invasive ovarian adenocarcinoma were treated on a phase II protocol of second-line intraperitoneal cisplatin, cytarabine, and bleomycin. All 31 patients received first-line intravenous (IV) cisplatin-based chemotherapy; the size of the residual cancer was documented surgically before intraperitoneal chemotherapy in all patients. Response to intraperitoneal chemotherapy was documented by a third-look laparotomy in all patients not evidencing progression of disease clinically. There were eight responses (26%): five surgical complete responses and three surgical partial responses. Responders were patients with stage III ovarian cancer, small residual disease of less than or equal to 1 cm (primarily less than or equal to 5 mm), and patients who previously had responded to cisplatin-based IV chemotherapy. Of the 15 patients with stage III ovarian cancer, residual disease less than or equal to 1 cm, and those who had responded to first-line IV cisplatin-based chemotherapy, 53% (eight) responded to second-line intraperitoneal chemotherapy. Intraperitoneal chemotherapy as used in this phase II protocol would appear to be an effective second-line treatment in advanced ovarian cancer in this specific subset of patients.
The systemic administration of intravenous melphalan.
Authors: Sarosy G , Leyland-Jones B , Soochan P , Cheson B D
Published: February 2017

Melphalan (L-phenylalanine mustard) is a bifunctional alkylating agent that is commonly administered orally to treat a wide variety of malignancies, including cancers of the breast and ovary, as well as multiple myeloma. Although commercially available in Europe and Canada, intravenous (IV) melphalan remains investigational in the United States. The role of IV melphalan in cancer chemotherapy is not well defined, despite its manageable toxicity and higher and more predictable blood levels following IV administration compared with oral administration. In addition, unlike oral melphalan, an extensive phase I evaluation of IV melphalan has not been undertaken. At lower doses (eg, 30 to 70 mg/m2), both as a single agent and in combination, the activity of IV melphalan has been evaluated in only a limited number of diseases. However, striking activity has been observed in previously untreated patients with rhabdomyosarcoma, a disease not generally considered responsive to alkylating agents. When administered at high doses (greater than 140 mg/m2) requiring bone marrow reinfusion, melphalan effects a high response rate (but no improvement in survival) in a variety of nonhematologic tumor types, including resistant tumors such as melanoma and colon carcinoma. In contrast, in poor-prognosis patients with non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or neuroblastoma, high-dose melphalan-containing regimens have yielded both high response rates and improved survival, despite considerable toxicity. Additional clinical trials will be necessary to define the spectrum of activity of lower doses of IV melphalan and to define subgroups of patients most likely to benefit from high-dose melphalan.
Combination chemotherapy with mastectomy or radiotherapy for stage III breast carcinoma: a Cancer and Leukemia Group B study.
Authors: Perloff M , Lesnick G J , Korzun A , Chu F , Holland J F , Thirlwell M P , Ellison R R , Carey R W , Leone L , Weinberg V
Published: February 2017

One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide (CYC), doxorubicin (DOX), 5-fluorouracil (5-FU), vincristine (VCR), and prednisone (PRED) (CAFVP). Subsequently, 91 (81%) were deemed operable. Patients were then randomized to receive surgery or radiotherapy (RT) to determine which of these modalities afforded better local tumor control. All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases. Forty-one of the randomized patients have relapsed. Approximately half of the initial relapses in each arm were local. The overall duration of disease control was similar following either modality, with a median of 29.2 months for surgery patients and 24.4 months for RT patients. Similarly, there was no major difference in survival related to randomized treatment with an overall median of 39 months (median follow-up 37 months). Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival. Treatment was generally well tolerated and toxicity was acceptable. This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor, using either surgery or RT. Nevertheless, new regimens must be designed if significant advances that may lead to the cure of this disease are to be achieved.
Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer.
Authors: Friedlander M L , Hedley D W , Swanson C , Russell P
Published: February 2017

The prognostic value of cellular DNA content in ovarian cancer (malignant common epithelial tumors) was investigated by flow cytometric analysis of paraffin-embedded tumor blocks from 128 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian cancer entered in a prospective clinical trial of combination v sequential therapy with chlorambucil and cisplatin. Seventy-three percent of tumors were aneuploid and 27% were diploid. Multivariate analysis using a Cox model showed that cellular DNA content (P less than .001) and FIGO stage (P less than .02) were the only significant independent prognostic variables. The median survival was 13 months for patients with aneuploid tumors and 60 months for patients with diploid tumors (P less than .0001). Further analysis indicated that the good prognosis associated with diploid tumors was limited to patients with stage III disease, all patients with stage IV (spread beyond the peritoneal cavity or liver metastases) disease having a poor prognosis irrespective of ploidy. On pathological review, nine borderline ovarian tumors (of low malignant potential) were identified, and seven of these were diploid. These tumors have an unusually favorable prognosis, despite apparent dissemination within the peritoneal cavity, a paradox which is often difficult to explain using conventional histological criteria. Although the vast majority of tumors in this study (93%) were classified as invasive epithelial ovarian cancers, it is possible that some of the patients with stage III diploid tumors may have had malignancies that were predominantly of low malignant potential, thus accounting in part for the prognostic significance of DNA content. By incorporating flow cytometric DNA analysis with careful histopathological assessment, it may be possible to better identify patients with an inherently good prognosis. This assumes particular importance, as the relatively favorable prognosis of patients with stage III diploid ovarian tumors appears to be independent of the type of treatment.
Patterns of failure in primary testicular non-Hodgkin's lymphoma.
Authors: Martenson J A , Buskirk S J , Ilstrup D M , Banks P M , Evans R G , Colgan J P , Earle J D
Published: February 2017

Patterns of failure were analyzed in 30 patients with testicular non-Hodgkin's lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management.
Factors affecting the prognosis of primary liver carcinoma.
Authors: Sutton F M , Russell N C , Guinee V F , Alpert E
Published: February 2017

Analysis of the clinical records of 163 patients with primary liver carcinoma was performed to identify factors affecting prognosis. The overall 3-year survival rate was 10%, and the median survival was 7.8 months. Survival was similar for patients with single or multiple tumor nodules. There was no significant association between nodule size of 3 cm or larger and survival. Patients who underwent resection had a longer survival. For patients without cirrhosis, location of the tumor in the left lobe regardless of whether it is resected appears to be a prognostic factor associated with prolonged survival. Female sex and the absence of cirrhosis were also associated with longer survival.
The prognostic importance of tumor size in malignant gliomas: a computed tomographic scan study by the Brain Tumor Cooperative Group.
Authors: Wood J R , Green S B , Shapiro W R
Published: February 2017

The prognostic importance of tumor size was studied in 510 patients with malignant glioma (80% with glioblastoma multiforme) in the Valid Study Group of Study 80-01 of the Brain Tumor Study Group (now the Brain Tumor Cooperative Group [BTCG]). The endpoint was length of survival from randomization, which occurred within 3 weeks of definitive surgery. Following randomization, patients were scheduled to receive radiotherapy (RT) (6,020 cGy) during a 7-week period, along with continuing courses of chemotherapy. Computed tomographic (CT) scan information was available for 124 patients preoperatively, 300 patients postoperatively (preradiation), and 218 patients 9 weeks post-RT (+/- 3 weeks). Tumor size was determined as area (length x width) on the contrast-enhanced scan and survival was compared by log rank statistics. Preoperative tumor area was unrelated to survival (P = .48), but postoperative area was significantly prognostic (P less than .0001); the smaller the residual tumor, the longer the patient lived. Patients with a 75% or greater resection, as determined by measuring the difference between the preoperative and the postoperative scans, tended to have better survival, but the difference was not significant (P = .16). The post-RT area was strongly related to survival (P less than .00001). The percent change in area between the pre- and post-RT scans was also prognostic. Tumor size was of prognostic importance independent of the other known prognostic variables: age, Karnofsky performance score, and whether the tumor was glioblastoma or anaplastic astrocytoma. We conclude that the amount of tumor remaining after surgery is an important baseline variable at the start of RT, and that the tumor size 9 weeks following RT is also prognostic. Surgical resection is most important when it leaves the least amount of residual tumor.
COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma.
Authors: Boyd D B , Coleman M , Papish S W , Topilow A , Kopel S K , Bernhardt B , Files J C , Schwartz S , Gaynor M , McDermott D
Published: February 2017

COPBLAM III, a polychemotherapy regimen consisting of cyclophosphamide, infusional vincristine, prednisone, infusional bleomycin, doxorubicin, and procarbazine, was administered to 51 patients with diffuse large-cell lymphoma. Ninety-six percent of patients age 60 or younger achieved a complete response (CR); none have relapsed. Overall, 88% of patients are alive and well and potentially in the survival plateau. For patients greater than 60 years, CR was obtained in 73%, with 42% potentially in the survival plateau, the difference resulting in part from four relapses, three toxic deaths, and one presumed unrelated death. These results in the elderly were paralleled by a relatively reduced ability to tolerate therapy. Toxicity was primarily pulmonary, occurring in 39% of patients, two of whom died. With an overall CR rate of 84%, of which 92% are sustained at a median follow-up of 40 months, COPBLAM III represents a highly effective treatment in a sizeable cohort of patients.
Phase II study of 10-ethyl-10-deaza-aminopterin in patients with stage III and IV non-small-cell lung cancer.
Authors: Shum K Y , Kris M G , Gralla R J , Burke M T , Marks L D , Heelan R T
Published: February 2017

10-ethyl-10-deaza-aminopterin (10-EDAM) is an analog of methotrexate that differs from its compound by modification of the N10 position and demonstrates greater preclinical antitumor activity and less toxicity. In this phase II trial, 20 patients with stage III or IV non-small-cell lung cancer (NSCLC) were administered 10-EDAM at a dose of 80 mg/m2 once weekly for 5 weeks. No patient had previously received chemotherapy. Nineteen of the 20 patients were adequately treated for response assessment. Six of 19 patients (32%) experienced a major objective response (exact 95% confidence limits, 15% to 55%). The median duration of response has not been reached and will exceed 13 months. Mucositis was the most common toxicity observed. Leukopenia was seen in only 10%, and 15% had platelet nadirs less than 100,000/microL. At the dosage and schedule used, 10-EDAM is an active agent in patients with NSCLC who are previously untreated with chemotherapy with a predicted response rate greater than or equal to 15% (P = .05). Because of its level of antitumor activity and the fact that 10-EDAM causes minimal myelosuppression, it is a suitable agent for further study in combination with other chemotherapeutic agents in this disease.
A mathematical model of drug resistance applied to treatment for small-cell lung cancer.
Authors: Gregory W M , Birkhead B G , Souhami R L
Published: February 2017

A mathematical model has been applied to patients with small-cell lung cancer (SCLC) in order to estimate the proportions of resistant and sensitive tumor at presentation, and the efficacy of the treatment, measured in terms of proportions of tumor killed with each cycle of therapy. The model uses estimates of tumor volume obtained from computed tomographic (CT) scans of the chest before each course of chemotherapy. Application of the model to a trial using single-agent high-dose cyclophosphamide (HDC) showed that HDC killed approximately 94% of the sensitive tumor on each application, but that the proportion of tumor resistant to HDC rose from an average of 1% to an average of 15% after the first cycle, assuming a 30-day tumor doubling time. These estimates proved fairly insensitive to different assumptions about tumor doubling time and inaccuracies in volume measurement and may thus provide a useful additional evaluation technique for some clinical trials.
Non-small-cell lung cancer: should unresectable stage III patients routinely receive high-dose radiation therapy?
Authors: Payne D G
Published: February 2017

Non-small-cell lung cancer patients who have unresectable mediastinal disease have a poor prognosis regardless of therapy administered. The various rationales for high-dose radiation therapy with curative intent are reviewed in the context of treatment results reported in the literature. The case for a dose-cure relationship in a clinically practical dose range must be considered unproven. On the other hand, the evidence for dose-response effects suggests that higher dosages could result in improved quality of life. There is a need to further refine reproducible criteria, both anatomic (such as mediastinal involvement) and non-anatomic (such as performance status), to permit more appropriate selection of patients for high-dose treatment. Studies involving less rather than more treatment with appropriate endpoints might be both ethical and appropriate.
Sequential versus alternating chemotherapy and radiotherapy in stage III-IV squamous cell carcinoma of the head and neck: a phase III study.
Authors: Merlano M , Rosso R , Sertoli M R , Bonelli L , Margarino G , Grimaldi A , Benasso M , Gardin G , Corvó R , Scarpati D
Published: February 2017

A cooperative randomized study was begun in August 1983 to compare a sequential program of induction chemotherapy followed by definitive treatment, arm A, with an alternation of chemotherapy and radiotherapy (three courses of 20 Gy in ten daily fractions), arm B. The same chemotherapy was used in both arms: 6 mg/m2, vinblastine, hour 0; 30 mg, bleomycin, hour 6; 200 mg, methotrexate, hours 24 to 26; 45 mg, leucovorin, hour 48. One hundred sixteen patients entered the study, 55 in arm A and 61 in arm B. The patients all had previously untreated squamous cell carcinoma of the head and neck (SCCHN). Forty-five patients had stage III and 71 had stage IV disease. The two arms were fully comparable. As of April 1986, 116 patients were evaluable for survival, while 112 were evaluable for toxicity and 105 for response. Response analysis shows that there were 14 complete responses (CR) and 11 partial responses (PR), for an overall response rate (ORR) of 52% in arm A, and 30 CRs and seven PRs, for an ORR of 64.9% in arm B. The difference in terms of CR between the two arms was statistically significant (P less than .03). Progression-free survival (PFS) was also statistically different, with an advantage for arm B (P less than .05), but without differences in overall survival. Arm B correlates with a significant increase in mucositis compared with arm A (P less than .001).
An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.
Authors: Pavlovsky S , Corrado C , Santarelli M T , Saslavsky J , Cavagnaro F , Palau M , de Tezanos Pinto M , Huberman A , Lein J M
Published: February 2017

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.
Squamous cell carcinoma antigen as a marker for squamous cell carcinoma of the anal canal.
Authors: Petrelli N J , Shaw N , Bhargava A , Daufeldt J , Herrera L , Stulc J P , Sischy B , Mittelman A
Published: February 2017

Twenty-one patients with documented squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 101 serum samples for radioimmunoassay of SCC antigen to evaluate regression or progression of disease. Eighteen presented with primary SCC of the anal canal, two with metastatic disease, and one with a recurrence in the perineum. Median follow-up was 18 months. Thirteen of 22 serum samples were true-positives, and nine of 22 were false-negatives. Four of 79 serum samples were false-positives and 75 of 79 were true-negatives. The sensitivity of this test is 59% and the specificity is 95%, with the accuracy of a positive test being 76%.
Assessing the effect of toxicity on prognosis: methods of analysis and interpretation.
Authors: Propert K J , Anderson J R
Published: February 2017

There has recently been an increased interest in and reporting of the association between toxicity and treatment outcome in cancer clinical trials. Such comparisons may be used to suggest mechanisms by which cytotoxic agents function in the cancer patient, especially regarding the importance of the effect of dose on the individual patient. However, analyses of "time-to-failure" outcomes such as survival by toxicity are subject to bias due to the time-dependence of both the predictor and outcome variables. In addition, interpretation of even appropriately conducted statistical analyses is problematic, as with analyses of survival by outcome variables such as response. The use of statistical methodology designed to avoid such biases in these comparisons is shown and the problems in the interpretation of results are discussed.
Chromosome studies in the non-Hodgkin's lymphomas: the role of the 14;18 translocation.
Authors: Rowley J D
Published: February 2017

The 14;18 translocation [t(14;18)] is the most common chromosome abnormality noted in the non-Hodgkin's lymphomas (NHL). Although the translocation is seen in various histologic subtypes, it is most commonly associated with the follicular lymphomas, especially the small-cleaved cell (FSC) and mixed-cell (FM) subtypes. The translocation breakpoint has been cloned and DNA probes from the junction on chromosome 18 can now be used to detect the genetic consequences of the translocation in tumors with few dividing cells. This will allow a more precise classification of this subset of lymphomas and should lead to better understanding of the biology of this category of lymphomas. Finally, these insights will help in the development of more effective and possibly less toxic therapy.
Effectiveness and Tolerability of Low-Dose Cyclophosphamide and Low-Dose Intravenous Interleukin-2 Disseminated Melanoma
Authors: Mitchell Malcolm S. , Kempf Raymond A. , Harel William , Shau Hungyi , Boswell William D. , Lind Susan , Bradley Edward C.
Published: February 2017

The title of the article by Mitchell et al published in the March 1988 issue (6:409–424) should have read "Effectiveness and Tolerability of Low-Dose Cyclophosphamide and Low-Dose Intravenous Interleukin-2 in Disseminated Melanoma." The word "in" was erroneously left out.
The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma.
Authors: Piver M S , Lele S B , Marchetti D L , Baker T R , Tsukada Y , Emrich L J
Published: February 2017

Forty consecutive patients with stage III and IV invasive ovarian carcinoma were treated on a phase II protocol consisting of optimal debulking surgery, induction cisplatin, cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy, 6-month interval laparoscopy, reinduction cisplatin, PAC chemotherapy, and second-look procedure. All 40 patients have either disease progression or have completed the 12-month protocol. Eighty-seven percent of the patients (35) underwent optimal (less than or equal to 2 cm residual) debulking surgery before chemotherapy, in spite of the fact that 50% (20) were referred to Roswell Park Memorial Institute (RPMI) as inoperable after initial surgery elsewhere. There were no postoperative deaths and chemotherapy was started in less than or equal to 14 days in 97% of the patients. Of the 40 patients, 30% (12) achieved a pathologic complete remission (11) or a clinical complete remission (one patient refused second-look surgery). The estimated 3-year survival rate was 62%, but the 3-year progression-free survival rate was only 29%. The median survival time was 48 months. The estimated 3-year progression-free survival rate was 31% for residual disease less than or equal to 2 cm. For the five patients with residual disease greater than 2 cm, four died within 3 years. The median survival time of patients with less than or equal to 2 cm residual disease was 48 months, as compared with 21 months for those with greater than 2 cm residual disease. Although the estimated 3-year survival rate of 62% is noteworthy, the 3-year progression-free survival rate of only 29% is probably indicative that in spite of extensive debulking surgery and cisplatin-based chemotherapy as used in this protocol, the long range proportion of patients "cured" will remain small.
An intensive, five course, alternating combination chemotherapy induction regimen used in patients with advanced, unresectable head and neck cancer.
Authors: Ensley J , Kish J , Tapazoglou E , Jacobs J , Weaver A , Atkinson D , Ahmed K , Mathog R , Al-Sarraf M
Published: February 2017

Progress in the treatment of advanced squamous cell cancer (SCC) of the head and neck (H & N) has included the development of combination chemotherapeutic regimens that achieve impressive complete response (CR) rates using two to three courses therapy with minimal toxicity and good patient tolerance. Further improvements in these results will require intensification of induction regimens. Therefore, a five course, alternating combination chemotherapy induction trial was initiated in an attempt to test the feasibility and toxicity of a prolonged, intensive induction regimen in patients with advanced SCC of H & N. Courses 1, 3, and 5 consisted of fluorouracil as a 120-hour infusion (5FU-I) with cisplatin (CACP) as an intravenous (IV) bolus. Courses 2 and 4 consisted of 3 weekly doses of high-dose methotrexate (HDMTX) followed by 5FU (5FU-b) and leucovorin rescue (LR). Forty-six stage IV patients with SCC of H & N (85% T4 and 58% N3) were entered. Thirty-one patients completed the study and 15 did not. Twenty-one of the 46 patients (46%) achieved a CR. Twenty-five of the 46 patients had N3 neck disease, ten of these 25 achieved a CR (40%), and eight did not complete therapy. Of the 15 patients not completing this study, one patient achieved a CR and eight achieved a partial response (PR). Eight of 46 (17%) were removed from study for reasons of toxicity (6% to 13%) or tumor progression (2% to 4%). The remaining seven were removed due to intercurrent medical conditions (four uncomplicated pneumonias and one gun shot wound) or lost to follow-up (2). Myelosuppression, mucositis, and skin toxicity increased in frequency by the end of the trial but were acceptable and reversible. The activity of this five-course regimen is promising given the advanced disease status of patients treated. Consideration of concurrent medical conditions, patient compliance, intensity of medical, nutritional and social support, and levels of acceptable toxicity will be necessary in the design of future, intensive induction trials.
Improvement of long-term survival in extensive small-cell lung cancer.
Authors: Jackson D V , Case L D , Zekan P J , Powell B L , Caldwell R D , Bearden J D , Nelson E C , Muss H B , Cooper M R , Richards F
Published: February 2017

The effect of adding the epipodophyllotoxin etoposide (VP-16-213) to a standard chemotherapy regimen for patients with extensive stage small-cell lung cancer was evaluated during a randomized trial. Chemotherapy consisted of vincristine, doxorubicin, and cyclophosphamide (VAC) alone or with etoposide (EVAC). Of 139 patients enrolled, 136 patients were eligible for study and all but five were evaluable for response. The overall objective response was 46% in the VAC group v 70% in the etoposide-treated group (P = .008) with complete response (CR) rates of 12% v 29%, respectively (P = .030). Although the time to the observation of disease progression was significantly longer in the group of patients receiving etoposide (9.6 v 6.5 months, P = .010), overall survival was similar; this was probably due to administration of other agents including etoposide at the time of VAC failure. However, there were noteworthy differences in long-term (greater than or equal to 2 year) survival. Whereas only four (6%) patients treated with VAC lived 2 years, 11 (16%) of the etoposide-treated group did so (P = .100). Two-year failure-free survival was attained in one (2%) of the VAC patients and eight (11%) of the patients treated with etoposide (P = .034). Long-term survivorship, heretofore usually reported in patients with limited stage disease after a variety of treatments, may be possible with this drug combination in the setting of extensive disease.
Human plasma pharmacokinetics of thiotepa following administration of high-dose thiotepa and cyclophosphamide.
Authors: Ackland S P , Choi K E , Ratain M J , Egorin M J , Williams S F , Sinkule J A , Bitran J D
Published: February 2017

Thiotepa is an established alkylating agent whose pharmacokinetics in standard doses are well defined. In order to ascertain whether dose-dependent variations in pharmacokinetics occur, we have undertaken an analysis of plasma thiotepa levels in 16 patients entered on a phase I-II study of bialkylator chemotherapy. High-dose thiotepa (1.8 to 7.0 mg/kg) and cyclophosphamide (2.5 g/m2) were administered intravenously (IV) on days -6, -4, and -2 followed by autologous marrow reinfusion on day 0. Plasma and urinary thiotepa was assayed by gas chromatography. Biexponential plasma decay curves were seen in ten patients, with a t 1/2 alpha of 10.0 +/- 6.4 minutes, a t 1/2 beta of 174 +/- 61 minutes and a total body clearance of 379 +/- 153 mL/h/kg (mean +/- SD). Six patients displayed monoexponential plasma decay curves with a terminal t 1/2 of 137 +/- 83 minutes and a total body clearance of 440 +/- 195 mL/h/kg. Although there was a trend toward reduced plasma clearance in the three patients treated at the highest dose level, the available data suggest that metabolic clearance mechanisms for thiotepa were not saturated with the doses used in this study. By stepwise regression analysis, linear functions using only 15-minute and four-hour postinfusion plasma levels were derived that correlated closely with area under the plasma concentration X time curves (AUC) (P less than .002). We conclude that high-dose thiotepa results in similar pharmacokinetic values to conventional doses with no apparent dose-dependent variation. The value of specific time points to predict AUC and clearance will require prospective evaluation.
Perioperative blood transfusions and cancer recurrence.
Authors: Wu H S , Little A G
Published: February 2017

This collective review addresses the issue of transfusion-induced immunosuppression as it relates to patients undergoing cancer surgery. Patients receiving perioperative blood transfusions have a significantly worse prognosis than patients undergoing cancer surgery without a perioperative transfusion. It is thought that this is because transfusions produce a nonspecific immunosuppression by increasing the number and/or activity of suppressor T lymphocytes, decreasing the number of natural killer cells, and inducing anti-idiotypic antibodies. This risk, particularly when considered with the other risks of transfusion such as hepatitis or the acquired immunodeficiency syndrome (AIDS), suggests that criteria for transfusion of these patients should be stringent and related to an unequivocal need for replenishment of RBCs.