bluuebunny/crossref_metadata_2025 huggingface dataset:
Complications of venous access ports in 132 patients with disseminated testicular cancer treated with polychemotherapy.
Authors: Lemmers N W , Gels M E , Sleijfer D T , Plukker J T , van der Graaf W T , de Langen Z J , Droste J H , Koops H S , Hoekstra H J
Published: February 2017

PURPOSE

Venous access ports (VAPs) can be used to administer polychemotherapy to patients with malignancies. The purpose of this study was to evaluate perioperative and late complications related to VAP implantations and to analyze factors that may predict the development of complications.

PATIENTS AND METHODS

During the period 1983 to 1994, 135 VAPs were implanted in 132 patients with disseminated testicular tumors. In a retrospective study, the perioperative and late complications were recorded in this homogeneous patient group. Multivariate analysis was performed to detect factors that may predict the development of complications.

RESULTS

The median age of the patients was 28 years (range, 16 to 55). Perioperative complications were recorded in five patients (3.7%): pneumothorax in two (1.5%), blood loss in two (1.5%), and mediastinal bleeding in one (0.7%). The ports remained in situ for a total of 55,247 days (median, 413; range, 7 to 1,607). In 31 patients (23%), 42 late complications developed (31%): system obstruction in 13 (9.6%), thrombosis in 11 (8.1%), infection in six (4.4%), catheter defect in six (4.4%), extravasation in four (3.0%), and local skin necrosis in two (1.5%). Late complications were significantly more common in patients who had received chemotherapy before VAP implantation (P < .001). Univariate analysis showed that there were significantly more complications after VAP implantation under local anesthesia than under general anesthesia (P < .05).

CONCLUSION

Polychemotherapy could be administered in an adequate manner using a VAP. Complications occurred in 26.7% of a homogeneous group of patients who received a VAP implantation for polychemotherapy for disseminated testicular cancer. Chemotherapy treatment before VAP implantation was the only independent risk factor for late complications.
Low cholesterol and cancer.
Authors: Kritz H , Zielinski C , Sinzinger H
Published: February 2017

PURPOSE

The relation between plasma cholesterol (CH) concentration and mortality is complex. The plasma CH concentration correlates positively with mortality from coronary heart disease, but some studies have shown a negative relation with death from cancer. If these two relations reflect causal mechanisms that are reversible by changing the plasma CH concentration, the benefits of lipid reduction for heart disease might be offset by an increased mortality from cancer. Different aspects between lipid metabolism and cancer, as well as new insights into this interesting field, are discussed.

METHODS

The literature was searched using MedLine through 1966 and January 1996.

RESULTS

There is no evidence from the data available at present that the association between low CH and a higher risk of cancer is causal.

CONCLUSION

This issue should not affect the advice on health matters offered by doctors, especially to patients with other risk factors for cardiovascular disease. The possibility that hypercholesterolemia (HC) drugs can induce a reduction of tumor-cell growth makes them potentially useful as an adjuvant to chemotherapy and ultimately increases the probabilities in the prevention and treatment of cancer.
Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase.
Authors: Baker S D , Khor S P , Adjei A A , Doucette M , Spector T , Donehower R C , Grochow L B , Sartorius S E , Noe D A , Hohneker J A , Rowinsky E K
Published: February 2017

PURPOSE

To study the absolute bioavailability and pharmacokinetics of an oral solution of fluorouracil (5-FU) in patients treated with 776C85, an oral inactivator of dihydropyrimidine dehydrogenase (DPD), and to evaluate the feasibility of administering oral 5-FU and 776C85 on a multiple-daily dosing schedule.

PATIENTS AND METHODS

Twelve patients with refractory solid tumors were enrolled onto this three-period study. In periods 1 and 2, patients were randomly assigned to treatment with 5-FU 10 mg/m2 on day 2 given by either the oral or intravenous (IV) route with oral 776C85 3.7 mg/m2/d on days 1 and 2. In period 3, patients received escalating doses of 5-FU (10 to 25 mg/ m2/d) orally for 5 days (days 2 to 6) with 776C85 3.7 mg/m2/d orally (days 1 to 7) every 4 weeks. Pharmaco-kinetic studies were performed in periods 1 and 2, and after the fifth oral dose of 5-FU in period 3.

RESULTS

Twelve patients completed the bioavailability and pharmacokinetic studies. Following oral 5-FU 10 mg/m2, the bioavailability was 122% +/- 40% (mean +/- SD), the terminal half-life (t1/2 beta) was 4.5 +/- 1.6 hours, the apparent volume of distribution (V beta) was 21.4 +/- 5.9 L/ m2, and the systemic clearance (Clsys) was 57.6 +/- 16.4 mL/min/m2. A correlation was observed between oral 5-FU systemic clearance and calculated creatinine clearance (r = .74; P = .009). Multiple-daily dosing did not appear to affect the pharmacokinetics of oral 5-FU. Neutropenia was the principal toxicity of oral 5-FU and 776C85, precluding escalation of oral 5-FU to doses greater than 25 mg/m2/d for 5 days every 4 weeks with 776C85.

CONCLUSION

The oral DPD inactivator 776C85 enables oral administration of 5-FU and may alter conventional 5-FU administration practices.
Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer.
Authors: Venturini M , Michelotti A , Del Mastro L , Gallo L , Carnino F , Garrone O , Tibaldi C , Molea N , Bellina R C , Pronzato P , Cyrus P , Vinke J , Testore F , Guelfi M , Lionetto R , Bruzzi P , Conte P F , Rosso R
Published: February 2017

PURPOSE

Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity.

PATIENTS AND METHODS

One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units.

RESULTS

One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms.

CONCLUSION

Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.
Prospective comparison of the sclerosing agents doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac tamponade.
Authors: Liu G , Crump M , Goss P E , Dancey J , Shepherd F A
Published: February 2017

PURPOSE

To compare the clinical efficacy and toxicity of doxycycline and bleomycin as sclerosing agents in the primary management of malignant pericardial effusion (MPE).

METHODS

Twenty-seven consecutive adult patients referred to a tertiary-care institution for the management of cardiac tamponade and malignancy underwent pericardial drainage through a percutaneously placed pigtail catheter. They were then alternately assigned to undergo bleomycin or doxycycline pericardial sclerosis.

RESULTS

There were 13 men and 14 women, with a median age of 59 years. They mainly had lung (70%) and breast cancers (11%), and all had clinical and echocardiographic evidence of cardiac tamponade. Although all patients had successfully placed catheters, six were inadvertently dislodged before sclerosis; 11 underwent bleomycin sclerosis and 10 doxycycline sclerosis. Twenty patients (one early death) were assessable. One patient in each group failed to respond to sclerosis with the initial agent, but both were sclerosed successfully with the other agent. Sclerosis was achieved with a median of two instillations for each agent and total median doses of bleomycin 20 mg and doxycycline 1,250 mg. Seventy percent of doxycycline patients developed significant retrosternal pain, compared with no bleomycin patients (P = .04). Doxycycline patients required a median of 3.5 more days of hospitalization (8.5 v 5) and 2 more days of pericardial catheterization (7 v 5) compared with bleomycin patients. Tamponade recurred in one bleomycin patient at 253 days, and in no doxycycline patient.

CONCLUSION

Although bleomycin and doxycycline are equally effective sclerosing agents, bleomycin is associated with significantly less morbidity and should be the first-line chemical sclerosing agent for malignant pericardial effusions.
nm23 in ovarian cancer: correlation with clinical outcome and other clinicopathologic and biochemical prognostic parameters.
Authors: Scambia G , Ferrandina G , Marone M , Benedetti Panici P , Giannitelli C , Piantelli M , Leone A , Mancuso S
Published: February 2017

PURPOSE

The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients.

PATIENTS AND METHODS

Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody.

RESULTS

Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles.

CONCLUSION

The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.
Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.
Authors: Pujade-Lauraine E , Guastalla J P , Colombo N , Devillier P , François E , Fumoleau P , Monnier A , Nooy M , Mignot L , Bugat R , Marques C , Mousseau M , Netter G , Maloisel F , Larbaoui S , Brandely M
Published: February 2017

PURPOSE

The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy.

PATIENTS AND METHODS

One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy.

RESULTS

Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted.

CONCLUSION

These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.
Effect of tamoxifen on endometrial proliferation.
Authors: Decensi A , Fontana V , Bruno S , Gustavino C , Gatteschi B , Costa A
Published: February 2017

PURPOSE

An increase in the incidence of endometrial cancer and a potential increase in related mortality has been associated with the administration of 20 mg tamoxifen, the dose adopted in breast cancer chemoprevention trials, thus urging studies on intermediate markers of risk.

PATIENTS AND METHODS

Thirty-three women who received 20 mg tamoxifen as adjuvant breast cancer treatment underwent endometrial biopsy. Samples were divided for histologic examination, including a quantitative analysis of stromal:epithelial ratio, and an assessment of DNA ploidy and proliferation by flow cytometry. Results were compared with 37 symptomatic subjects.

RESULTS

All histograms were DNA diploid. Compared with controls, a significant increase in the risk of proliferation as measured by the hyperdiploid fraction was associated with tamoxifen duration (< or = 36 months: cumulative odds ratio = 16.5, 95% confidence interval, 1.85 to 146.5; > 36 months: cumulative odds ratio = 28.2, 95% confidence interval, 2.56 to 310.6, P for trend < .05). Tamoxifen-induced risk was significantly reduced by the extent of menopausal status. No cases of cancer or epithelial hyperplasia were observed in the tamoxifen group, whereas seven cases of epithelial hyperplasia without atypia were observed in the control group. The effect of tamoxifen on proliferation was associated with an increase in the stromal component.

CONCLUSION

Tamoxifen at 20 mg/d exerts a time-dependent proliferative effect on the endometrium, particularly in premenopausal and early postmenopausal women. This effect appears to be mediated by the stromal component, which accounts for the discrepancy between flow cytometry and histology. Our study provides preliminary evidence that the DNA flow cytometric hyperdiploid fraction may be a useful tool for monitoring endometrial cell proliferation in women exposed to tamoxifen.
Adjuvant chemotherapy for high-risk clinical stage I nonseminomatous testicular germ cell cancer: long-term results of a prospective trial.
Authors: Pont J , Albrecht W , Postner G , Sellner F , Angel K , Höltl W
Published: February 2017

PURPOSE

To assess the impact of short-term adjuvant chemotherapy on relapse rates, treatment-related morbidity, and long-term toxicity in patients with clinical stage I nonseminomatous testicular germ cell tumor (NSGCT I) who carry a high risk of relapse, ie, who show blood-vessel invasion (VI) by the primary tumor.

PATIENTS AND METHODS

From January 1985 to January 1995, 42 NSGCT I patients with VI were treated with two courses of cisplatin, etoposide, and bleomycin (PEB) after orchidectomy. Of these, 29 patients with a follow-up time of more than 2 years are the subject of this report. NSGCT I patients without VI were assigned to a surveillance program and served as controls for the assessment of long-term toxicity.

RESULTS

During a median follow-up time of 79 months (range, 27 to 119), two patients relapsed. One developed fully differentiated mature teratoma; the other was a true chemotherapy failure and again developed embryonal carcinoma. Twenty-seven patients (93%) are alive without evidence of disease; one patient (3%) died of progressive testicular cancer and another of lung cancer. The two courses of PEB did not cause any severe acute adverse reactions. The assessment of late sequels of adjuvant chemotherapy based on clinical and laboratory evidence of cardiovascular and pulmonary disease, fertility, and secondary neoplasms, as well as on a psychosocial questionnaire, did not show any significant disadvantages versus the control group.

CONCLUSION

Adjuvant chemotherapy with two courses of PEB is an effective and reasonable treatment option for patients with clinical stage I NSGCT who carry a high risk of relapse. No adverse late sequelae were detected within a median follow-up time of more than 6 years.
Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma.
Authors: Wallner K , Roy J , Harrison L
Published: February 2017

PURPOSE

To quantify disease progression and morbidity following computer tomography (CT)-based transperineal iodine 125 prostate implantation.

METHODS

Ninety-two patients with clinical stage T1 or T2, Gleason score 2 to 7/10, prostatic carcinoma had outpatient, CT-based transperineal 125I prostate implantation and were monitored for 1 to 7 years (median, 3). The prescribed minimum radiation dose was 140 to 160 Gy. Lymph node dissection and postimplantation prostatic biopsies were not routinely performed.

RESULTS

In 46% of patients, radiation-related urinary symptoms were substantial enough at 1 month following implantation to require medication. Radiation-related urinary symptoms gradually resolved. Two years after implantation, 14% of patients had persistent urinary symptoms of Radiation Therapy Oncology Group (RTOG) > or = grade 2. Eight percent of patients underwent a transurethral resection of the prostate (TURP) within 2 years of implantation. Five patients developed radiation-induced rectal ulcerations. Of 56 patients who were sexually potent preimplantation, 86% retained potency at 3 years. Twenty-five patients had biochemical disease progression. The overall actuarial freedom from biochemical failure rate at 4 years following implantation was 63%. In Cox proportional hazards multivariate analysis, the strongest predictor of failure was prostate-specific antigen (PSA) level less than or greater than 10 ng/mL (P = .005), followed by Gleason score (2 to 4 v 5 to 7, P = .08) and stage (T1 v T2, P = .09).

CONCLUSION

The 5-year biochemical freedom-from-progression rates following transperineal 125I implantation are comparable with those achieved with prostatectomy. The morbidity has decreased with increased physician experience.
The value of high-dose methotrexate-based neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone.
Authors: Ham S J , Hoekstra H J , van der Graaf W T , Kamps W A , Molenaar W M , Schraffordt Koops H
Published: February 2017

PURPOSE

The value of high-dose methotrexate (HD-MTX)-based neoadjuvant chemotherapy was evaluated in patients with malignant fibrous histiocytoma (MFH) of bone.

PATIENTS AND METHODS

Since 1977, MFH of bone was diagnosed in 17 patients (12 males and five females). Ten patients (59%), completed treatment with four courses of neoadjuvant chemotherapy as follows: HD-MTX, vincristine, doxorubicin, cyclophosphamide, bleomycin, and dactinomycin, or HD-MTX, 4(1)-epidoxorubicin, and carboplatin followed by local tumor resection (n = 3), curettage-cryosurgery (n = 2), amputation (n = 2), or tumor resection-endoprosthetic replacement or allograft (n = 3). After recovery from surgery, an additional six courses of polychemotherapy, including HD-MTX in nine patients, were administered. One patient changed to cisplatin- instead of HD-MTX-containing chemotherapy postoperatively. One additional patient received only adjuvant HD-MTX-containing polychemotherapy. Neoadjuvant MTX-containing chemotherapy was contraindicated in five patients (29%) due to age, cardiac insufficiency, or mental disorder. In one patient, neoadjuvant chemotherapy was cancelled after one course due to renal failure. Treatment consisted of amputation (n = 2), one course of chemotherapy and amputation (n = 1), hyperthermic isolated limb perfusion (HILP; n = 1), intraarterial chemotherapy, radiotherapy, and endoprosthetic replacement (n = 1), and a combination of chemotherapy and radiation treatment (n = 1).

RESULTS

Five of six patients who received no HD-MTX-based neoadjuvant chemotherapy developed metastatic disease (83%); the median time to metastatic disease was 17 months (range, 3 to 44). In contrast, in 10 patients who completed treatment with HD-MTX-based neoadjuvant chemotherapy, with a mean follow-up time of 9.8 years (range, 2.3 to 15.7) and a median follow-up time of 10.8 years (range, 2.3 to 15.7) after diagnosis, no local recurrence or distant metastases were diagnosed (P < .005).

CONCLUSION

Neoadjuvant HD-MTX-containing chemotherapy in addition to surgery has dramatically improved the prognosis of patients with MFH of bone.
Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06.
Authors: Schultz C , Scott C , Sherman W , Donahue B , Fields J , Murray K , Fisher B , Abrams R , Meis-Kindblom J
Published: February 2017

PURPOSE

This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL).

PATIENTS AND METHODS

Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy.

RESULTS

As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients.

CONCLUSION

Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.
Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.
Authors: Miralbell R , Bieri S , Mermillod B , Helg C , Sancho G , Pastoors B , Keller A , Kurtz J M , Chapuis B
Published: February 2017

PURPOSE

To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT).

PATIENTS AND METHODS

From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI). Seventy-nine patients with normal renal function before conditioning are included in this study. Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell depletion was undertaken in 48 cases. The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L. The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed.

RESULTS

The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%. Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis. The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively.

CONCLUSION

Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.
Survival benefit from high-dose therapy with autologous blood progenitor-cell transplantation in poor-prognosis non-Hodgkin's lymphoma.
Authors: Pettengell R , Radford J A , Morgenstern G R , Scarffe J H , Harris M , Woll P J , Deakin D P , Ryder D , Wilkinson P M , Crowther D
Published: February 2017

PURPOSE

To compare standard and intensive treatment strategies for patients with high-grade non-Hodgkin's lymphoma (NHL) of poor prognosis, defined by the international prognostic index.

PATIENTS AND METHODS

Thirty-four patients received standard chemotherapy with 11 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone, and methotrexate (VAPEC-B), and 33 received intensive treatment with 7 weeks of VAPEC-B, three cycles of ifosfamide/cytarabine, then high-dose busulfan/cyclophosphamide followed by autologous blood progenitor-cell (BPC) transplantation.

RESULTS

Twelve of 33 patients in the intensive group and 26 of 34 patients in the standard group have died. The median follow-up time for the surviving patients is 31 months and 68 months, respectively. At 2 years, the actuarial estimates of event-free survival (EFS) were 61% versus 35% (P = .01) and of overall survival, 64% versus 35% (P = .01). A significant reduction in the event rate (progression or death) was maintained after adjustment for age and the number of risk factors. The estimated risk of experiencing an event was 0.37 (95% confidence interval [CI], 0.16 to 0.84) in the intensive group compared with the standard group.

CONCLUSION

Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS. The survival differences observed in this study justify a formal comparison in a randomized study.
Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.
Authors: Vellenga E , Uyl-de Groot C A , de Wit R , Keizer H J , Löwenberg B , ten Haaft M A , de Witte T J , Verhagen C A , Stoter G J , Rutten F F , Mulder N H , Smid W M , de Vries E G
Published: February 2017

PURPOSE

To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever.

PATIENTS AND METHODS

One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period).

RESULTS

Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05).

CONCLUSION

These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.
ZD1694: A novel thymidylate synthase inhibitor with substantial activity in the treatment of patients with advanced colorectal cancer. Tomudex Colorectal Study Group.
Authors: Zalcberg J R , Cunningham D , Van Cutsem E , Francois E , Schornagel J , Adenis A , Green M , Iveson A , Azab M , Seymour I
Published: February 2017

PURPOSE

Tomudex (ZD1694; Zeneca Ltd, Macclesfield, United Kingdom) appears to have a favorable toxicity profile (defined in phase I studies) and antitumor activity in a broad range of epithelial tumors. We report here the results of a large phase II study of Tomudex in advanced colorectal cancer (CRC).

PATIENTS AND METHODS

One hundred seventy-seven patients were entered onto the study between October 1992 and September 1993. Patients were required to have advanced CRC without prior chemotherapy (adjuvant chemotherapy was permissible) and at least one measurable lesion. Tomudex (ZD1694) was administered at a dose of 3 mg/m2 intravenously once every 3 weeks in the absence of toxicity or disease progression. Patients were assessed for objective response, progression, and survival.

RESULTS

Of 177 patients entered onto the study, 5% had received prior adjuvant chemotherapy and 83% had liver metastases. Objective responses were seen in 26% of patients (95% confidence interval, 19% to 33%; four complete responses [CRs] and 41 partial responses [PRs]) while median time to progression was 4.2 months and median survival 9.6 months. All sites were audited, and responses were reviewed by an independent panel. Common toxicities included mild reversible transaminitis, nausea and vomiting, and asthenia or flu-like symptoms, and World Health Organization (WHO) grade 3 and 4 leukopenia and diarrhea were seen in 6% and 9.8% of patients, respectively. Stomatitis and alopecia were common.

CONCLUSION

In this large multicenter phase II study of patients with advanced CRC, interesting activity was seen (objective response rate, 26%). In addition, Tomudex has an acceptable toxicity profile and a convenient dosing schedule (single intravenous injection every 3 weeks) and thus appears to offer real potential as a novel agent for the treatment of patients with advanced CRC.
Combined liver radiation and chemotherapy for palliation of hepatic metastases from colorectal cancer.
Authors: Mohiuddin M , Chen E , Ahmad N
Published: February 2017

PURPOSE

To report the effects of boost dose radiation on palliation, survival, and toxicity in patients undergoing palliative treatment for hepatic metastases from colorectal cancers and to assess the potential benefits of higher doses of radiation to partial liver volumes.

MATERIALS AND METHODS

Forty-five patients with hepatic metastases from colorectal cancers were treated with a course of palliative irradiation. Eligible patients included those with radiographically or histologically proven liver metastases. All patients but one received chemotherapy, either pretreatment (one patient) and/or concurrently with radiation (43 patients) via intravenous or hepatic intraarterial infusion. Patients were divided into two groups based on whether or not boost radiation was given. Thirty-three of the 45 patients (group 1) received whole-liver irradiation at doses that ranged from 8 to 31 Gy at 2.0 to 3.0 Gy per fraction (median dose, 21 Gy). The remaining 12 patients (group 2) received liver irradiation to 20 to 30 Gy followed by a boost dose to the area of dominant disease for a total dose of 33 to 60 Gy. The extent of liver involvement was similar between the two groups. Palliation, overall survival, and toxicity were analyzed with respect to radiation dose.

RESULTS

There was no increase in acute effects observed in treating partial liver volumes to higher doses in conjunction with systemic chemotherapy. No cases of radiation-induced hepatitis or nephritis were documented. Hematologic toxicity (> or = grade 3) was observed in four patients with thrombocytopenia, three with leukopenia, and two with anemia. Pain was relieved in 71% and hepatomegaly in 59% of group 1 patients, as compared with 100% and 89%, respectively, of group 2 patients. Other symptoms such as nausea, fever, fatigue, and jaundice were palliated in 35% of group 1 and 90% of group 2 patients. The median survival time for group 1 patients was 4 months (range, 1 week to 26 months), which is consistent with that reported in the literature. The median survival time for group 2 patients was 14 months (range, 2 to 32 months) (P=.01).

CONCLUSION

Standard hepatic irradiation followed by boost radiation to partial liver volumes in combination with chemotherapy is well tolerated without significant acute/late morbidity. Higher radiation doses to partial liver volumes offers improved palliative benefit and may prolong survival without an increase in morbidity.
Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.
Authors: Baselga J , Tripathy D , Mendelsohn J , Baughman S , Benz C C , Dantis L , Sklarin N T , Seidman A D , Hudis C A , Moore J , Rosen P P , Twaddell T , Henderson I C , Norton L
Published: February 2017

PURPOSE

Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer.

PATIENTS AND METHODS

We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk.

RESULTS

Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months.

CONCLUSION

rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.
Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine.
Authors: Johnson B E , Bridges J D , Sobczeck M , Gray J , Linnoila R I , Gazdar A F , Hankins L , Steinberg S M , Edison M , Frame J N , Pass H , Nesbitt J , Holden D , Mulshine J L , Glatstein E , Ihde D C
Published: February 2017

PURPOSE

A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival.

PATIENTS AND METHODS

Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen.

RESULTS

Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years.

CONCLUSION

This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.
Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region. A meta-analysis of prospective and randomized trials.
Authors: El-Sayed S , Nelson N
Published: February 2017

PURPOSE

Using the technique of meta-analysis, we aim to illustrate the potential benefit, or lack of it, in adding chemotherapy to locoregional definitive treatment in a prospective randomized setting.

PATIENTS AND METHODS

Mantel-Haenszel summary analyses were used to test 42 prospective and properly randomized trials for statistically significant differences in the proportion with side effects and in the proportion with response to treatment between the experimental treatment arm (including chemotherapy) and control arm (local definitive treatment only) of the study. Summarized estimates of relative risks of side effects and relative proportions of positive responses were obtained using the summarizing options in PROC FREQ in the SAS computer package. In 25 of 42 studies, sufficient survival information was available to estimate the effect of chemotherapy on the rate of dying per person per unit of time.

RESULTS

Chemotherapy, when added to local definitive treatment, was found to increase toxicity. This increase is statistically significant. The relative proportion of side effects was 2.17, with a 95% confidence interval of 1.84 to 2.56 and P less than .001. Addition of chemotherapy to local treatment has reduced the mortality rate for treated patients by 11% in the total group (all 25 studies), with a 95% confidence interval of 1% to 19%. This reduction means that at the time 50% of patients in the control arm were still alive, 54% of patients who received chemotherapy would be expected to be alive. Concurrent treatment (11 studies) has reduced the mortality rate by 22%, with a 95% confidence interval of 8% to 33%, which means that at the time 50% of patients in the control arm were still alive, 58% of patients who received chemotherapy would be expected to be alive.

CONCLUSION

Addition of chemotherapy to local definitive treatment has significantly increased the morbidity of treatment as well as the chance of initial tumor response and local control. A statistically significant improvement in survival was found for the simultaneous use of chemotherapy and local definitive treatment.
Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma.
Authors: Pisters P W , Harrison L B , Leung D H , Woodruff J M , Casper E S , Brennan M F
Published: February 2017

PURPOSE

This trial was performed to evaluate the impact of adjuvant brachytherapy on local and systemic recurrence rates in patients with soft tissue sarcoma.

PATIENTS AND METHODS

In a single-institution prospective randomized trial, 164 patients were randomized intraoperatively to receive either adjuvant brachytherapy (BRT) or no further therapy (no BRT) after complete resection of soft tissue sarcomas of the extremity or superficial trunk. The adjuvant radiation was administered by iridium-192 implant, which delivered 42 to 45 Gy over 4 to 6 days. The two study groups had comparable distributions of patient and tumor factors, including age, sex, tumor site, tumor size, and histologic type and grade.

RESULTS

With a median follow-up time of 76 months, the 5-year actuarial local control rates were 82% and 69% in the BRT and no BRT groups (P = .04), respectively. Patients with high-grade lesions had local control rates of 89% (BRT) and 66% (no BRT) (P = .0025). BRT had no impact on local control in patients with low-grade lesions (P = .49). The 5-year freedom-from-distant-recurrence rates were 83% and 76% in the BRT and no BRT groups (P = .60), respectively. Analysis by histologic grade did not demonstrate an impact of BRT on the development of distant metastasis, despite the improvement in local control noted in patients with high-grade lesions. The 5-year disease-specific survival rates for the BRT and no BRT groups were 84% and 81% (P = .65), respectively, with no impact of BRT regardless of tumor grade.

CONCLUSION

Adjuvant brachytherapy improves local control after complete resection of soft tissue sarcomas. This improvement in local control is limited to patients with high-grade histopathology. The reduction in local recurrence in patients with high-grade lesions is not associated with a significant reduction in distant metastasis or improvement in disease-specific survival.
P-glycoprotein expression at diagnosis may not be a primary mechanism of therapeutic failure in childhood rhabdomyosarcoma.
Authors: Kuttesch J F , Parham D M , Luo X , Meyer W H , Bowman L , Shapiro D N , Pappo A S , Crist W M , Beck W T , Houghton P J
Published: February 2017

PURPOSE

To evaluate the prognostic significance of tumor cell P-glycoprotein (Pgp) expression at diagnosis in children with rhabdomyosarcoma.

PATIENTS AND METHODS

A panel of three anti-Pgp monoclonal antibodies (mAb) (C219, C494, and JSB-1) that recognize different Pgp epitopes was used to measure Pgp expression in rhabdomyosarcoma specimens obtained at diagnosis from 76 patients treated at St Jude Children's Research Hospital from 1969 to 1991. Two separate experiments using different immunohistochemical methods (immune alkaline phosphatase and immunoperoxidase) were performed to evaluate Pgp expression. The immunostaining was graded using a semiquantitative scale corresponding to the percentage of tumor cells with detectable staining. The influence of Pgp expression on outcome was assessed by the Kaplan-Meier method and Cox regression analysis with stepwise selection. The relationship between Pgp expression and clinical features was assessed using the Mantel-Haenszel method.

RESULTS

Pgp expression at diagnosis did not predict worse overall survival or progression-free survival when tested in either experiment with C219, C494, or JSB-1 separately. No association was shown between Pgp expression and clinical features (clinical group, primary site, or histology) or response. However, in the immune alkaline phosphatase experiment, patients whose tumors had more than 10% tumor cell staining with all three mAbs had a significantly higher rate of estimated 5-year survival (78% +/- 10%) than did all other patients (38% +/- 8%; P = .025). In this instance, Pgp expression had independent prognostic value after adjusting for clinical group.

CONCLUSION

We found no strong association between Pgp expression at diagnosis and clinical features or extent of disease in pediatric rhabdomyosarcoma. Depending on the criteria used to define it, high Pgp expression at diagnosis does not predict poor outcome. Although a large prospective study is needed to provide definitive conclusions, our findings suggest that Pgp-mediated multidrug resistance may not be a primary mechanism of therapeutic failure in rhabdomyosarcoma.