bluuebunny/crossref_metadata_2025 huggingface dataset:
Low specificity of cytokeratin 19 reverse transcriptase-polymerase chain reaction analyses for detection of hematogenous lung cancer dissemination.
Authors: Krismann M , Todt B , Schröder J , Gareis D , Müller K M , Seeber S , Schütte J
Published: February 2017

PURPOSE

Sensitive detection of systemic tumor dissemination in lung cancer patients is important for selection of appropriate treatment modalities. Based on recent promising data that showed reverse transcriptase-polymerase chain reaction (RT-PCR) analyses for cytokeratin 19 (CK-19) expression in peripheral-blood or bone marrow samples to be a rapid and highly sensitive method for detection of hematogenous tumor dissemination in patients with breast and prostate cancer, we evaluated the specificity of this assay system in lung cancer patients and a large number of healthy controls.

PATIENTS AND METHODS

We examined CK-19 mRNA expression by RT-PCR in 17 lung cancer cell lines and in peripheral-blood samples of 50 lung tumor patients and 65 healthy controls.

RESULTS

Expression of CK-19 mRNA was observed in all lung cancer cell lines and in 50% of peripheral-blood samples from lung tumor patients. However, under the experimental conditions analyzed, at least 20% of the control samples were positive for CK-19 mRNA expression.

CONCLUSION

Contrary to prior reports, RT-PCR may detect non-tissue-specific constitutive low-level (illegitimate) expression of CK-19 mRNA in peripheral-blood mononuclear (PBMN) cells in a significant number of healthy controls. This finding may not only hamper the use of this assay system in lung cancer patients, but also questions its proposed applicability in patients with other epithelial tumors such as breast and prostate cancer.
Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer.
Authors: Ravdin P M , Burris H A , Cook G , Eisenberg P , Kane M , Bierman W A , Mortimer J , Genevois E , Bellet R E
Published: February 2017

PURPOSE

The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone.

PATIENTS AND METHODS

Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen.

RESULTS

Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively).

CONCLUSION

Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.
Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.
Authors: Valero V , Holmes F A , Walters R S , Theriault R L , Esparza L , Fraschini G , Fonseca G A , Bellet R E , Buzdar A U , Hortobagyi G N
Published: February 2017

PURPOSE

To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC).

PATIENTS AND METHODS

Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days.

RESULTS

Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively.

CONCLUSION

Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.
Association of malignant brain tumors and cancers of other sites.
Authors: Ahsan H , Neugut A I , Bruce J N
Published: February 2017

PURPOSE

We conducted an exploratory study of brain tumors that occurred as a second primary malignancy to identify potential risk factors for brain tumors.

METHODS

Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated the sex-specific standardized incidence ratio (SIR), adjusted to age and time period, as an estimate of the relative risk (RR) of developing a second primary brain tumor following other cancers.

RESULTS

We found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7; 95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to 3.2); this effect was present for both astrocytoma and glioblastoma multiforme. Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8 to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0 to 1.9) in women. The highest RR observed in this study was for CNS lymphoma following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0).

CONCLUSION

The associations of brain tumors with bladder, colorectal, and endometrial cancers in women, and an increased occurrence of CNS lymphoma as a second malignancy in men, are new findings that have not been described previously.
Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelodysplasia.
Authors: O'Donnell M R , Long G D , Parker P M , Niland J , Nademanee A , Amylon M , Chao N , Negrin R S , Schmidt G M , Slovak M L
Published: February 2017

PURPOSE

A non-radiation-containing regimen of busulfan and cyclophosphamide (BU/CY) was evaluated for toxicity, relapse, and long-term survival in patients who received allogeneic bone marrow transplantation (BMT) for myelodysplasia (MDS).

PATIENTS AND METHODS

Thirty-eight patients with MDS, including eight with therapy-related MDS, were prepared for BMT using BU/CY.

RESULTS

Fourteen patients remain in first remission 18 to 60 months posttransplant. Five patients relapsed after BMT, and four of these patients died. Eight additional patients died of acute or chronic graft-versus-host disease (GVHD), and 11 died of regimen-related toxicity, primarily systemic mycoses. Overall survival rate at 2 years was 45% (95% confidence interval [CI], 0.30 to 0.61), with a 24% probability of relapse (95% CI, 0.10 to 0.49). Regimen-related toxicity was manifested primarily as hepatic dysfunction in 72% of patients, with 16% developing overt venoocclusive disease (VOD).

CONCLUSION

Non-radiation-containing preparative regimens offer long-term survival in allogeneic BMT for MDS that is comparable to that of radiation-containing regimens, and are useful in patients with therapy-related MDS. Monitoring BU levels may reduce regimen-related mortality and improve survival.
Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-Münster Group.
Authors: Reiter A , Schrappe M , Parwaresch R , Henze G , Müller-Weihrich S , Sauter S , Sykora K W , Ludwig W D , Gadner H , Riehm H
Published: February 2017

PURPOSE

To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL).

PATIENTS AND METHODS

From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression.

RESULTS

The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure.

CONCLUSION

This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.
Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.
Authors: Ung O , Langlands A O , Barraclough B , Boyages J
Published: February 2017

PURPOSE

This retrospective review examines local control, freedom from distant failure, and survival for patients with nonmetastatic breast cancer with extensive nodal disease (> 10 nodes, 45 patients; or > or = 70% involved nodes, if < 10 nodes found, 19 patients). All patients received chemotherapy and radiotherapy following mastectomy.

PATIENTS AND METHODS

Sixty-four patients were treated between January 1980 and December 1988 at Westmead Hospital, Westmead, NSW Australia. The median follow-up duration for surviving patients was 91.5 months (range, 56 to 121). The median age was 51 years, and the median number of positive nodes was 11. Four successive protocols evolved, each with three phases, as follows: induction chemotherapy (doxorubicin or mitoxantrone, plus cyclophosphamide; three cycles), radiotherapy (50 Gy in 25 fractions to chest wall and regional nodes), then chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen.

RESULTS

One patient (1.5%) developed local recurrence before distant relapse, and seven patients (11%) developed local and/or regional recurrence simultaneously or after distant relapse. The 5-year actuarial freedom from distant relapse and overall survival rates were 45% and 65%, respectively. Overall survival did not vary significantly by menopausal status, nodal subgroup, or dose-intensity. There were no treatment-related deaths.

CONCLUSION

Combined chemotherapy and radiotherapy in standard dosage is an acceptable approach following mastectomy for patients with extensive nodal involvement at high risk for local recurrence and distant relapse. This approach should be considered standard best therapy for any randomized trials that examine high-dose chemotherapy or bone marrow transplantation for this subgroup of patients.
Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma.
Authors: Younes A , Sarris A , Melnyk A , Romaguera J , McLaughlin P , Swan F , Rodriguez M A , Hagemeister F , Moore D , North L
Published: February 2017

PURPOSE

Paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is a novel antimicrotubule agent with anti-tumor activity against ovarian and breast carcinomas. Its activity when administered as a 3-hour intravenous infusion in patients with relapsed non-Hodgkin's lymphoma (NHL) has not been studied.

PATIENTS AND METHODS

Patients with relapsed NHL were treated with a 3-hour infusion of 200 mg/m2 of Taxol every 3 weeks in an outpatient setting. All patients received premedication (dexamethasone, diphenhydramine, and cimetidine) to prevent allergic reactions. Responses were assessed after two courses of therapy, and patients who achieved at least partial remission (PR) continued to receive Taxol for a maximum of eight courses.

RESULTS

Of 60 eligible patients, 54 (90%) were assessable for treatment toxicity and 53 (88%) were for treatment response (22 with primary refractory and 31 with relapsed disease). Twelve patients (23%) achieved a PR (n = 6) or complete remission (CR; n = 6) (95% confidence interval, 12% to 36%). Responses were observed in intermediate-grade (31%), low-grade (14%), and mantle-cell (17%) lymphomas. In the intermediate-grade lymphomas, there was a trend for a higher response rate in relapsed versus primary refractory disease (54% v 13%; P = .08). Treatment-related toxicity included alopecia (100%), peripheral neuropathy (37%), myalgia or arthralgia (25%), and neutropenic fever (11%). None of the patients had allergic reactions or cardiac toxicity.

CONCLUSION

At this dose and schedule, Taxol is an active agent in patients with relapsed NHL and can be safely administered in an outpatient setting. Combination programs with Taxol should be investigated for treatment of NHL.
Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.
Authors: Beaty O , Hudson M M , Greenwald C , Luo X , Fang L , Wilimas J A , Thompson E I , Kun L E , Pratt C B
Published: February 2017

PURPOSE

We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics.

PATIENTS AND METHODS

Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy.

RESULTS

At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy.

CONCLUSION

Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.
The Third Intergroup Rhabdomyosarcoma Study.
Authors: Crist W , Gehan E A , Ragab A H , Dickman P S , Donaldson S S , Fryer C , Hammond D , Hays D M , Herrmann J , Heyn R
Published: February 2017

PURPOSE

The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation.

PATIENTS AND METHODS

One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984).

RESULTS

The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III.

CONCLUSION

Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.
Double-blind, placebo-controlled, dose-response trial of oral clodronate in patients with bone metastases.
Authors: O'Rourke N , McCloskey E , Houghton F , Huss H , Kanis J A
Published: February 2017

PURPOSE

Despite evidence that clodronate inhibits tumor-induced osteolysis, no studies have directly assessed the optimal dose for long-term treatment. The aim of this double-blind, placebo-controlled study was to determine the safety and efficacy of different doses of clodronate in affected patients.

PATIENTS AND METHODS

Eighty-four patients with tumor-induced osteolysis were randomized to receive treatment with placebo, or 400 mg, 1,600 mg, or 3,200 mg of clodronate, daily for 4 weeks. Patients were reviewed weekly during treatment. Fasting urinary calcium excretion was the primary variable used to assess response. Visual analog pain scores and adverse events were documented.

RESULTS

In the clodronate-treated groups, there was a dose-dependent reduction in fasting calcium excretion with a highly significant difference between placebo and 1,600 mg clodronate (P = .0002) and placebo and 3,200 mg clodronate (P = .0001), but no significant difference between 1,600 mg and 3,200 mg clodronate. There was no discernible change in pain scores or analgesic requirements. Bone-derived isoenzyme alkaline phosphatase values increased in all groups, with a significant difference between baseline and final values in the 1,600-mg and 3,200-mg groups (P < .01 and P = .03, respectively). Adverse events were distributed evenly across the four treatment groups. Compliance was greater than 99% in all treatment groups.

CONCLUSION

Oral clodronate at a dose of 1,600 mg or 3,200 mg will inhibit bone resorption. Since there was no significant difference between these two doses in terms of efficacy at 4 weeks, 1,600 mg/d can be recommended for long-term treatment. This dose is well tolerated and may promote bone repair, as judged by increases in bone alkaline phosphatase levels.
Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial.
Authors: Klumpp T R , Mangan K F , Goldberg S L , Pearlman E S , Macdonald J S
Published: February 2017

PURPOSE

It is well-established that the infusion of hematopoietic growth factors (HGF) accelerates neutrophil recovery in patients undergoing high-dose therapy followed by autologous bone marrow infusion. In addition, there is evidence that the infusion of autologous peripheral-blood stem cells (PBSC) accelerates engraftment in comparison to patients who receive bone marrow alone. However, few data are available regarding the ability of HGF to accelerate engraftment further in patients who receive PBSC following high-dose therapy.

PATIENTS AND METHODS

Forty-one patients undergoing high-dose therapy followed by infusion of autologous PBSC with or without bone marrow were randomized to receive granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d beginning on day + 1 following transplant or standard posttransplant supportive care without HGF.

RESULTS

The median time to a neutrophil count > or = 500/microL was 10.5 days in the G-CSF group versus 16 days in the control group (P = .0001). G-CSF was associated with statistically significant reductions in the time to neutrophil engraftment among patients who received PBSC alone (11 v 17 days, P = .0003) and in patients who received PBSC in conjunction with bone marrow (10 v 14 days, P = .02). The median duration of posttransplant hospitalization (18 v 24 days, P = .002) and the median number of days on nonprophylactic antibiotics (11 v 15, P = .03) were also significantly reduced.

CONCLUSION

Administration of G-CSF in the posttransplant period accelerates the rate of neutrophil engraftment, shortens the duration of hospitalization, and reduces the number of days on nonprophylactic antibiotics in patients who receive autologous PBSC with or without autologous bone marrow following high-dose therapy.
Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison.
Authors: Beyer J , Schwella N , Zingsem J , Strohscheer I , Schwaner I , Oettle H , Serke S , Huhn D , Stieger W
Published: February 2017

PURPOSE

To compare autologous bone marrow (BM) with peripheral-blood progenitor cells (PBPC) as hematopoietic rescue after high-dose chemotherapy (HDCT).

PATIENTS AND METHODS

From January 1991 until April 1993, 47 consecutive patients with relapsed or refractory germ cell tumors were randomized to either BM harvest or collection of PBPC mobilized by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). After additional conventional-dose salvage treatment, all patients received HDCT with carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 with either BM or PBPC rescue.

RESULTS

Forty-six patients were assessable for hematologic reconstitution, and one patient died on day +4 before engraftment. Rescue using PBPC resulted in a significantly shorter recovery time to neutrophil counts more than 500/microL (10.0 v 11.0 days, P < .01), neutrophil counts more than 1,000/microL (10.0 v 12.0 days, P = .001), and platelet counts more than 20,000/microL (10.0 v 17.0 days, P < .01), as well as in fewer days to transfusion independence from RBCs (8.0 v 12.0, P < .05) and platelets (9.0 v 12.0, P < .01) and fewer days of intravenous (IV) antibiotics (9.0 v 11.0, P < .05). However, no statistical differences in transfusion requirements or in other clinical outcome variables were observed. Overall survival and event-free survival also were not different in the two study arms.

CONCLUSION

We conclude that the use of PBPC mobilized by chemotherapy plus G-CSF results in sustained trilineage reconstitution after HDCT, which occurs more rapidly as compared with BM. The earlier hematologic reconstitution in patients with PBPC rescue significantly reduces the time to transfusion independence.
Malignant germ cell tumors in men infected with the human immunodeficiency virus: natural history and results of therapy.
Authors: Timmerman J M , Northfelt D W , Small E J
Published: February 2017

PURPOSE

To determine how men infected with the human immunodeficiency virus (HIV) tolerate and respond to treatment for malignant germ cell tumors (GCTs), and how GCT histology and stage compare among HIV-infected versus non-HIV-infected men.

PATIENTS AND METHODS

Two hundred ninety-four cases of GCT diagnosed or treated from 1980 to 1993 were reviewed. Nine new cases among HIV-infected men were identified; these were analyzed together with six cases previously reported from our institution.

RESULTS

Low-stage tumors (stages I and IIA) comprised 67% of HIV-infected and 63% of non-HIV-infected cases. Sixty-seven percent of HIV-infected cases were seminomas versus 51% of non-HIV-infected cases. Ten patients had AIDS at the time of GCT diagnosis. Five patients underwent radiation therapy and one patient underwent retroperitoneal lymphadenectomy without complications. Seven patients received chemotherapy with four cycles of cisplatin, etoposide, and bleomycin (PEB) or cisplatin, vinblastine, and bleomycin (PVB) without excess cytopenias or new opportunistic infections. Of seven patients treated for advanced disease, there were five complete and two partial responses. Six patients have died of AIDS at a median of 20 months after diagnosis of GCT. The median follow-up time for surviving patients has been 42 months (range, 8 to 87) and all but one remain without evidence of active disease. In no case was a patient's HIV disease classification altered by antitumor therapy.

CONCLUSION

The natural history of GCTs is comparable in HIV-infected and non-HIV-infected men and standard therapy including orchiectomy, retroperitoneal lymph node dissection, radiation therapy, and chemotherapy is well tolerated.
Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer.
Authors: Hainsworth J D , Levitan N , Wampler G L , Belani C P , Seyedsadr M S , Randolph J , Schacter L P , Greco F A
Published: February 2017

PURPOSE

This randomized phase II study evaluated the efficacy and toxicity of etoposide phosphate when used in combination with cisplatin in the treatment of small-cell lung cancer.

PATIENTS AND METHODS

Patients with previously untreated small-cell lung cancer were randomized to receive cisplatin in combination with either etoposide or etoposide phosphate. Molar-equivalent doses of etoposide and etoposide phosphate were used. Response rate, time to progression, survival, and toxicity were compared.

RESULTS

Major response rates with etoposide phosphate and etoposide were 61% (95% confidence interval, 55% to 67%) and 58% (95% confidence interval, 52% to 64%), respectively (P = .85). No significant differences in median time to progression or survival were observed in patients who received etoposide phosphate versus etoposide. Grade 3 and 4 leukopenia occurred in 63% of patients who received etoposide phosphate compared with 77% who received etoposide (P = .16).

CONCLUSION

The combination of etoposide phosphate and cisplatin is effective in the treatment of small-cell lung cancer, and can be administered with acceptable toxicity. Although this study was not designed to be a formal comparative trial, the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar-equivalent etoposide doses. Because of its greater ease of administration, etoposide phosphate is preferable to etoposide for routine clinical use.
Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experience.
Authors: Tallman M S , Gray R , Bennett J M , Variakojis D , Robert N , Wood W C , Rowe J M , Wiernik P H
Published: February 2017

PURPOSE

Since large numbers of patients with early-stage breast cancer now receive adjuvant chemotherapy containing cyclophosphamide, a known leukemogenic agent, it is important to determine the risk of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Therefore, we identified all cases of AML or MDS developing in patients treated on six clinical adjuvant chemotherapy trials conducted by the Eastern Cooperative Oncology Group (ECOG).

PATIENTS AND METHODS

The patients population included 2,638 patients with previously untreated primary operable breast cancer entered onto six clinical trials conducted by the ECOG between 1978 and 1987. There are 19,200 persons-years of follow-up study and a mean follow-up duration of 7.3 years. Clinical data were obtained from flow sheets submitted to the ECOG Data Management Office.

RESULTS

Of 2,638 patients at risk with 19,200 person-years of follow-up study, three patients developed MDS (two with a characteristic cytogenetic abnormality). Two patients developed acute leukemia; however, one had adult T-cell leukemia associated with human T-lymphotrophic virus type 1 (HTLV-1) and a second patient developed AML after receiving additional cyclophosphamide for metastatic breast cancer. The estimated incidence rate for MDS is three per 19,200 or 16 per 100,000 person-years of follow-up study with a 95 percent confidence interval of three to 46 per 100,000 person-years. If all five patients (three MDS and two acute leukemia) are included, the estimated incidence rate is five per 19,200 or 26 per 100,000 person-years of follow-up study with a 95 percent confidence interval of eight to 61 per 100,000 person-years.

CONCLUSION

These data suggest that the risk of secondary AML or MDS among patients with early breast cancer who receive standard-dose cyclophosphamide-containing adjuvant chemotherapy is not much higher than in the general population. However, physicians must remain alert to the possible long-term consequences of alkylating agent and anthracycline-based chemotherapy.
Perioperative blood transfusions do not affect disease recurrence of patients undergoing curative resection of colorectal carcinoma: a Mayo/North Central Cancer Treatment Group study.
Authors: Donohue J H , Williams S , Cha S , Windschitl H E , Witzig T E , Nelson H , Fitzgibbons R J , Wieand H S , Moertel C G
Published: February 2017

PURPOSE

To evaluate the effect of perioperative blood transfusions on colorectal cancer recurrence and patient survival.

PATIENTS AND METHODS

A total of 1,051 patients treated with curative surgery for stage II or III colorectal adenocarcinoma were retrospectively studied for the effect of perioperative blood transfusions on disease recurrence and patient survival. Forty-two percent of patients received perioperative blood components.

RESULTS

Perioperative transfusions had no effect on disease progression in univariate or multivariate analysis. Tumor stage (P = .0001), locally advanced tumor characteristics (adherence, involvement of adjacent structure, or perforation; P = .0001), location (rectal v colon; P = .0002), grade (P < .001), and cell kinetic profile (nondiploid or high percent synthetic phase [%S]+ percent gap 2 mitosis phase [%G2M]; P = .0003) were the most powerful independent predictors of tumor recurrence. Use of transfusions was associated with an adverse effect on overall survival (P < .004) using multivariate analysis, as well as tumor stage (P = .0001), location (P = .004), grade (P = .001), patient age (P = .0001), sex (P < .04), and cell kinetic profile (P = .0001). In further evaluation of the prognostic effects of transfusions, there was no increased risk of disease recurrence after whole-blood transfusion (P = .14) as compared with packed RBC or no transfusions, although the disease-specific survival for patients who received whole blood was lower than for nontransfused patients (P < .0005) patients who received other blood components (P < .03).

CONCLUSION

With transfusion practices that use blood components, most commonly RBCs, medically indicated transfusions to patients with colorectal carcinoma seem to have no impact on disease recurrence. The adverse impact of transfusions on cancer patient survival is more likely due to other unevaluated tumor variables or underlying illness rather than tumor recurrence enhancement by immunosuppression induced by transfusion of blood components.
Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: antitumor activity in a phase II trial and interactions in vitro.
Authors: Motzer R J , Schwartz L , Law T M , Murphy B A , Hoffman A D , Albino A P , Vlamis V , Nanus D M
Published: February 2017

PURPOSE

A phase II trial of interferon alfa-2a (IFN) and 13-cis-retinoic acid (CRA) was conducted in patients with renal cell carcinoma (RCC). In vitro studies were performed to investigate potential mechanisms of interaction.

PATIENTS AND METHODS

Forty-four patients were treated. IFN was given daily at 3 MU and escalated to 6 and 9 MU if tolerated. The dose of CRA was 1 mg/kg/d. The effects of combining CRA and IFN on the proliferation of five RCC cell lines were examined, and retinoid sensitivity was correlated to the expression of retinoic acid receptors.

RESULTS

Thirteen (30%) of 43 assessable patients achieved a major response (three complete and 10 partial). Responding sites included bone metastases and renal primary tumors. Seven responding patients remain progression-free at 10+ to 19+ months. The response proportion was higher than in our prior experience with IFN, which was 10% in 149 patients. Eleven of 12 renal cancer cell lines were resistant to CRA alone; one, SK-RC-06, showed 90% inhibition of cell growth. CRA augmented the antiproliferative effect of IFN in several IFN-sensitive cell lines, but not in IFN-resistant lines. Northern blot analysis showed that expression of retinoic acid receptor-beta (RAR-beta) was repressed and not induced by retinoic acid in retinoic acid-insensitive RCC lines. However, RAR-beta expression was induced by retinoic acid in SK-RC-06 cells.

CONCLUSION

IFN and CRA showed antitumor activity in patients with advanced RCC, and the proportion and nature of response suggested CRA added therapeutic benefit to IFN. A phase III randomized trial of IFN plus CRA versus IFN alone and a phase II trial of single-agent CRA have been initiated.
Tumor-associated proteolysis and prognosis: new functional risk factors in gastric cancer defined by the urokinase-type plasminogen activator system.
Authors: Heiss M M , Babic R , Allgayer H , Gruetzner K U , Jauch K W , Loehrs U , Schildberg F W
Published: February 2017

PURPOSE

The significance of tumor-associated proteolysis as reflected by parameters of the urokinase-type plasminogen activator (uPA) system for prognosis in cancer patients has been proposed because of evidence for its central role in basic mechanisms of invasion and metastasis. The aim of the present study was to evaluate whether the expression of the uPA parameters might be of clinical value in gastric cancer as a tumor/biologically defined risk factor.

PATIENTS AND METHODS

In a consecutive series of 203 patients resected for primary gastric cancer, the expression of uPA, uPA-receptor (uPA-R), plasminogen activator inhibitor (PAI)-1, and PAI-2 was determined immunohistochemically. The results were classified semiquantitatively (0 to 3). Patients were followed-up prospectively for a median of 31 months (range, 9 to 56 months). Disease-free and overall survival were analyzed according to Kaplan-Meier and with univariate and multivariate Cox analyses in relation to conventional prognostic factors.

RESULTS

Univariate analyses revealed a highly significant inverse correlation of uPA, uPA-R, and PAI-1 expression with survival time (P = .0008, P = .0002, and P = .0002, respectively), whereas PAI-2 demonstrated only a weak correlation. In multivariate analyses, PAI-1 was an independent and strong prognostic factor (P = .005; relative risk, 1.47 per staining degree; 95% confidence interval [CI], 1.31 to 1.64). In pT1/2 tumors and in Laurén's diffuse and mixed types, uPA, uPA-R, and PAI-1 added significant prognostic information. PAI-1 was also associated with survival in the subgroup of lymph node-positive patients.

CONCLUSION

PAI-1, uPA, and uPA-R are new functional risk factors reflecting clinical prognosis. In particular, PAI-1 is a new independent variable for the identification of patients at high risk after tumor resection. Our results support the hypothesis that the uPA system probably is of general importance for prognosis of patients with malignant disease, indicating an individual tumor's capacity for invasion and metastasis.
Role of computed tomography in the staging of patients with local-regional metastases of melanoma.
Authors: Buzaid A C , Tinoco L , Ross M I , Legha S S , Benjamin R S
Published: February 2017

PURPOSE

To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level.

PATIENTS AND METHODS

The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient.

RESULTS

Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules.

CONCLUSION

TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.
Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.
Authors: Morgan R J , Margolin K , Raschko J , Akman S , Leong L , Somlo G , Scanlon K , Ahn C , Carroll M , Doroshow J H
Published: February 2017

PURPOSE

To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA).

PATIENTS AND METHODS

Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d).

RESULTS

Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed.

CONCLUSION

CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA < or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.
Stage I testicular seminoma: results of adjuvant irradiation and surveillance.
Authors: Warde P , Gospodarowicz M K , Panzarella T , Catton C N , Sturgeon J F , Moore M , Goodman P , Jewett M A
Published: February 2017

PURPOSE

To assess the results of treatment and patterns of relapse in a contemporary group of patients with stage I testicular seminoma managed by adjuvant radiation therapy (RT) and surveillance.

PATIENTS AND METHODS

Between January 1981 and December 1991, 364 patients with stage I seminoma were treated at Princess Margaret Hospital. Of these, 194 were treated with adjuvant RT (92% received a dose of 25 Gy in 20 fractions for 4 weeks) and 172 were managed by surveillance. Two patients were included in this series twice--both had postorchiectomy RT for stage I disease, developed a contralateral seminoma, and were placed on surveillance and analyzed for outcome of both primary tumors. The median follow-up period for patients treated with adjuvant RT was 8.1 years (range, 0.2 to 12), and for patients managed by surveillance, it was 4.2 years (range, 0.6 to 10.1).

RESULTS

The overall 5-year actuarial survival rate for all patients was 97%, and the cause-specific survival rate was 99.7%. Only one patient died of seminoma. Of 194 patients treated with RT, 11 have relapsed, with a 5-year relapse-free rate of 94.5%. Prognostic factors for relapse included histology, tunica invasion, spermatic cord involvement, and epididymal involvement. Twenty-seven patients developed disease progression on surveillance, which resulted in a 5-year progression-free rate of 81.9%. The only factor identified to predict progression on surveillance was age at diagnosis: patients aged < or = 34 years had a 26% risk of progression at 5 years, in contrast to a 10% risk of progression in those greater than 34 years of age.

CONCLUSION

The outcome of patients with stage I testicular seminoma is excellent, with only one of 364 patients (0.27%) dying of disease. In our experience, both a policy of adjuvant RT and of surveillance resulted in a high probability of cure. Our surveillance experience showed that four of five patients with stage I seminoma are cured with orchiectomy alone. The benefit of adjuvant RT was reflected in a decreased relapse rate. We have identified a number of prognostic factors for relapse in patients managed with both approaches, but further study of prognostic factors is required, particularly to identify patients at high risk of disease progression on surveillance.
Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.
Authors: Stram D O , Matthay K K , O'Leary M , Reynolds C P , Haase G M , Atkinson J B , Brodeur G M , Seeger R C
Published: February 2017

PURPOSE

To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT).

METHODS

Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells.

RESULTS

One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%).

CONCLUSION

Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.