bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer.
Authors: Hayes D F , Van Zyl J A , Hacking A , Goedhals L , Bezwoda W R , Mailliard J A , Jones S E , Vogel C L , Berris R F , Shemano I
Published: February 2017

PURPOSE

To perform a randomized three-arm comparison of tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer.

MATERIALS AND METHODS

Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212).

RESULTS

The combined response rates (by intent to treat) were as follows;: TAM, 44%; TOR60, 50%; and TOR200, 48%. Complete and partial response rates were as follows: TAM, 19%; TOR60, 21%, and TOR200, 23% (not statistically different). Median times to progression and overall survival were not significantly different. Adverse events (lethal, serious but nonlethal, and important but non-life-threatening) were similar in all three arms, except that patients in the TOR200 arm had a statistically significantly increased rate of nausea (37% v 26% and 26% for TOR200, TAM, and TOR60, respectively; P = .027). Quality-of-life assessments were not different among the three arms.

CONCLUSION

The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of a dose-response effect for TOR. TOR60 is an effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients.
Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients.
Authors: Staal-van den Brekel A J , Dentener M A , Schols A M , Buurman W A , Wouters E F
Published: February 2017

PURPOSE

To determine whether an increased resting energy expenditure (REE) and weight loss in lung cancer patients are related to a systemic inflammatory response.

MATERIALS AND METHODS

REE was measured by indirect calorimetry using a ventilated hood system. Soluble tumor necrosis factor receptor 55 (sTNF-R55) and sTNF-R75, soluble intercellular adhesion molecule (sICAM)-1, soluble E (sE)-selectin, lipopolysaccharide (LPS)-binding protein (LBP), interleukin (IL)-6, and TNF-alpha were measured using sandwich enzyme-linked immunosorbent assay (ELISA), and C-reactive protein (CRP) was measured by turbidimetry. A cross-sectional study was performed to compare inflammatory mediators between hypermetabolic (REE/Harris Benedict [HB] equation > or = 110%) versus normometabolic (REE/HB < 110%) patients and between patients who lost weight (more than 10% loss of preillness weight) versus those whose weight remained stable.

RESULTS

Eighty-seven patients with primary non-small-cell lung cancer were consecutively entered onto the study. Mean REE expressed as a percentage of the HB reference values was 118% +/- 12%; 67 patients were considered hypermetabolic. Twenty-six patients had a substantial loss of more than 10% of their preillness weight. Hypermetabolic patients were found to have significantly increased levels of sTNF-R55, sE-selectin, LBP, and CRP compared with normometabolic patients. Weight loss was related with increased levels of the sTNF-Rs, sICAM-1, IL-6, LBP, and CRP.

CONCLUSION

Hypermetabolism and weight loss are related to the presence of a systemic inflammatory response as reflected by enhanced levels of inflammatory mediators and acute phase proteins in patients with primary non-small-cell lung cancer.
Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors.
Authors: Roach M , Gandara D R , Yuo H S , Swift P S , Kroll S , Shrieve D C , Wara W M , Margolis L , Phillips T L
Published: February 2017

PURPOSE

To identify factors associated with radiation pneumonitis (RP) resulting from combined modality therapy (CMT) for lung cancer.

MATERIALS AND METHODS

Series published before 1994 that used CMT for the treatment of lung cancer and explicitly reported the incidence of RP are the basis for this analysis. Factors evaluated included the radiation dose per fraction (Fx), total radiation dose, fractionation scheme (split v continuous), type of chemotherapy and intended dose-intensity, overall treatment time, histology (small-cell lung cancer [SCLC] v non-small-cell lung cancer [NSCLC]), and treatment schedule (concurrent v induction, sequential, or alternating CMT).

RESULTS

Twenty-four series, including 27 treatment groups and 1,911 assessable patients, met our criteria for inclusion in this analysis. The median total dose of radiation used in the trials analyzed was 50 Gy (range, 25 to 63 Gy). The median daily Fx used was 2.0 Gy (range, 1.5 to 4.0 Gy). Nineteen series included 22 treatment groups and 1,745 patients treated with single daily fractions. Among these patients, 136 received a daily Fx greater than 2.67 Gy. Five series used twice-daily radiotherapy and included 166 patients (Fx, 1.5 to 1.7 Gy). The incidence of RP was 7.8%. In a multivariate analysis, only daily Fx, number of daily fractions, and total dose were associated with the risk of RP (P < .0001, P < .018, and P < .003, respectively).

CONCLUSION

In this analysis, the use of Fx greater than 2.67 Gy was the most significant factor associated with an increased risk of RP. High total dose also appears to be associated with an increased risk, but twice-daily irradiation seems to reduce the risk expected if the same total daily dose is given as a single fraction. High-Fx radiotherapy should be avoided in patients who receive CMT with curative intent.
Doxifluridine and leucovorin: an oral treatment combination in advanced colorectal cancer.
Authors: Bajetta E , Colleoni M , Di Bartolomeo M , Buzzoni R , Bozzetti F , Doci R , Somma L , Cappuzzo F , Stampino C G , Guenzi A
Published: February 2017

PURPOSE

This study was designed to test the activity and feasibility of an all-oral regimen of levo-leucovorin and doxifluridine (dFUR) in the treatment of advanced colorectal cancer and to establish whether the pharmacokinetics of dFUR and fluorouracil (FU) are affected by demographic and/or biologic parameters.

MATERIALS AND METHODS

One hundred eight patients with histologically proven colorectal cancer received orally administered levo-leucovorin 25 mg followed 2 hours later by dFUR 1,200 mg/m2 on days 1 to 5, with the cycle being repeated every 10 days.

RESULTS

Among 62 previously untreated patients, two complete responses (CRs) and 18 partial responses (PRs) were observed (overall response rate, 32%; 95% confidence interval, 21% to 45%). The median response duration was 4 months (range, 2 to 13) and the median survival time, 14 months. Among 46 pretreated patients, there were three CRs and three PRs (response rate, 13%; 95% confidence interval, 5% to 26%). In this group of patients, the median response duration was 4 months (range, 1 to 12) and the median survival time, 12 months. No toxic deaths were observed. The only World Health Organization (WHO) grade 3 to 4 side effect was diarrhea (32 patients).

CONCLUSION

This regimen is active in previously untreated colorectal cancer patients and combines good compliance with safety. Limited but definite efficacy was also detected in the patients previously treated with FU, which suggests incomplete cross-resistance between the two drugs. The pharmacokinetic results suggest that the conversion rate of dFUR to FU increases between days 1 and 5, but that FU levels remain low in comparison to those measured after classical FU therapy. Under the experimental conditions used in this study, the interpatient variability of pharmacokinetic parameters remains largely unexplained by the tested variables.
Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study.
Authors: Gianni L , Munzone E , Capri G , Fulfaro F , Tarenzi E , Villani F , Spreafico C , Laffranchi A , Caraceni A , Martini C
Published: February 2017

PURPOSE

To define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy.

PATIENTS AND METHODS

Thirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of > or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles.

RESULTS

Severe neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 in 34 assessable patients. Grade II peripheral neuropathy occurred in 33% of patients. Six women (18%) developed clinically reversible congestive heart failure (CHF) after a median of 480 mg/m2 total DOX. Drug sequence had no effect on toxicities. High efficacy on all metastatic sites in 32 assessable patients accounted for a 41% complete response (CR) rate (95% confidence interval [CI], 24% to 59%) and 94% overall-response rate (95% CI, 79% to 99%). After a median follow-up of 12 months (range 3 to 18), the median response duration is 8 months (range, 2+ to 18+) for complete responders and 11 months (range 1+ to 15+) for partial responders.

CONCLUSION

The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial. Until clarification of this possibility, this promising combination should be used in investigational trials.
Randomized cooperative study of perioperative chemotherapy in breast cancer.
Authors: Sertoli M R , Bruzzi P , Pronzato P , Queirolo P , Amoroso D , Del Mastro L , Venturini M , Vigani A , Bertelli G , Campora E
Published: February 2017

PURPOSE

The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients.

PATIENTS AND METHODS

Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy.

RESULTS

At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing.

CONCLUSION

This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.
Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group.
Authors: Teodorovic I , Pittaluga S , Kluin-Nelemans J C , Meerwaldt J H , Hagenbeek A , van Glabbeke M , Somers R , Bijnens L , Noordijk E M , Peeters C D
Published: February 2017

PURPOSE

Before recognizing mantle-cell lymphoma (MCL) as a distinct entity, these patients were grouped into low-grade (LG) or intermediate-/high-grade categories (IGHG) according to the Working Formulation and received various therapies. This was a unique opportunity to evaluate characteristics, behavior, response to treatment, and outcome of patients with MCL from two phase III trials conducted by the European Organization for the Research and Treatment of Cancer (EORTC): EORTC 20855 IGHG and EORTC 20856 LG.

PATIENTS AND METHODS

After histologic review, 64 diagnosed MCL patients (29 IGHG and 35 LG) were compared with other patients in their respective trials. In the IGHG group, patients received cyclophosphamide, doxorubicin, teniposide (VM26), prednisone, vincristine, and bleomycin (CHVmP-VB) or modified doxorubicin, cyclophosphamide, etoposide (VP 16), mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE-MOPP). In the LG group, after receiving cyclophosphamide, vincristine, and prednisone (CVP) induction, patients were randomized between maintenance treatment with interferon alfa-2a (IFN) or no further treatment.

RESULTS

MCL patients compared with IGHG subtypes showed a similar overall survival and response rate, but shorter duration of response and progression-free survival. Comparing with LG patients, their response rate, duration of response, and progression-free survival showed no difference, while their overall survival was nearly twice shorter. MCL patients treated with CHVmP-VB had the longest survival. No treatment showed any significant improvement in terms of progression-free survival.

CONCLUSION

These data confirm that MCL represents a clinicopathologic entity. In terms of survival, it behaves like IGHG subtypes, while in terms of progression-free survival, it behaves like LG lymphoma. It is still not clear which first-line treatment offers patients with MCL the best chance to obtain both a complete response (CR) and a long-term survival.
Adequate locoregional treatment for early breast cancer may prevent secondary dissemination.
Authors: Arriagada R , Rutqvist L E , Mattsson A , Kramar A , Rotstein S
Published: February 2017

PURPOSE

To analyze different events that determine event-free survival (EFS) in a randomized trial on adjuvant radiotherapy in early breast cancer patients with more than 15 years of follow-up evaluation.

PATIENTS AND METHODS

The trial included 960 patients with a unilateral, operable breast cancer. Surgery consisted of a modified radical mastectomy. The trial compared three arms, as follows: preoperative radiotherapy, postoperative radiotherapy, and no adjuvant treatment. Events were analyzed by a competing-risk approach. A proportional hazards multiple regression model was used to analyze the effects of radiotherapy on the risk of distant metastasis. Similar analyses were performed separately for node-negative [N(-)] and node-positive [N(+)] patients in the two groups that did not include preoperative radiotherapy.

RESULTS

Radiotherapy produced a fivefold decrease of the risk of local recurrence (P < .0001). In N(+) patients, postoperative radiotherapy decreased the risk of distant dissemination (relative risk, 0.63). When local recurrence was introduced in the model as a time-dependent covariate, this factor was predictive of distant dissemination (P < .0001) and nullified the effect of postoperative radiotherapy. This finding suggests that the decrease of distant metastases was related to the prevention of local recurrence. A similar effect was found in models that used overall survival as an end point.

CONCLUSION

This study shows that postmastectomy radiotherapy in N(+) breast cancer patients may decrease the distant metastasis rate by preventing local recurrences and thus avoiding secondary dissemination.
Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control?
Authors: Leonard C E , Wood M E , Zhen B , Rankin J , Waitz D A , Norton L , Howell K , Sedlacek S
Published: February 2017

PURPOSE

To determine if a delay of irradiation to the intact breast for administration of adjuvant chemotherapy results in increased local recurrence in breast cancer.

PATIENTS AND METHODS

The records of 262 women with 264 cases of breast cancer were reviewed. Group I contained 105 patients treated with conservative surgery, chemotherapy, and radiotherapy. Group II contained 157 patients (used as a concurrent control) treated with conservative surgery and radiotherapy only. Eighty-nine percent of subjects in group I received all chemotherapy before radiotherapy. Fifty-eight percent of patients received hormone therapy. Seventy-one percent of patients had negative surgical margins, and 74% had negative lymph nodes. For group I, conservative surgery-radiotherapy intervals in months were less than 1 (five, 5%), > or = 1 to less than 3 (10, 9%), > or = 1 to less 6 (48, 46%), and > or = 6 (42, 40%), mean of 5. For group II, the intervals were less than 1 (20, 13%), > or = 1 to less than 3 (123, 79%), > or = 3 to less than 6 (11, 7%), and > or = 6 (two, 1%), mean of 1.5.

RESULTS

Thirty patients (11.5%) have disease recurrence (19 distant [6%] and 12 local [5%]). There were no significant differences in local recurrence (group I, four [4%]; group II, eight [5%]; difference not significant). There were no significant differences in local recurrence in any surgery-radiotherapy interval within each group. Although we found marginal increases in the percentage of local recurrences in group I patients (with prolonged surgery-radiotherapy intervals) who had positive margins, positive lymph nodes, and tumor size more than 2 cm versus group II (without prolonged surgery-radiotherapy intervals), these results were not significant.

CONCLUSION

We could not identify any surgery-radiotherapy interval that resulted in increased local recurrence if radiotherapy was delayed for administration of adjuvant chemotherapy in breast cancer patients. Because of the heterogenous population of breast cancer patients, our results also support the need for further study to determine the optimum integration of radiotherapy and chemotherapy in the management of the conservatively treated breast.
Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil.
Authors: Kerr D J , Ledermann J A , McArdle C S , Buckels J , Neoptolemos J , Seymour M , Doughty J , Budden J , Taylor I
Published: February 2017

PURPOSE

A phase I and pharmacokinetic trial was performed between October 1993 and June 1994 to determine the maximum-tolerated dose of hepatic arterial infusion (HAI) of fluorouracil (5-FU) and intravenous (IV) leucovorin (folinic acid; FA) in patients with hepatic metastases from colorectal cancer.

PATIENTS AND METHODS

Forty-three patients received 310 courses of HAI chemotherapy administered over 48 hours every 2 weeks. The regimen consisted of FA 200 mg/m2 by IV infusion over 2 hours, followed by a loading dose of 5-FU 400 mg/m2 by HAI over 15 minutes, followed by a 22-hour infusion of 5-FU at doses ranging from 0.8 to 1.84 g/m2, with identical chemotherapy on day 2. Pharmacokinetic studies were performed to determine peak and steady-state plasma concentrations (Css) of 5-FU.

RESULTS

Severe diarrhea and cardiac and neurologic toxicity were dose-limiting at 1.84 g/m2. The recommended dose for the 22-hour component of the schedule was 1.6 g/m2 and was associated with tolerable toxicity. A Css of 2.2 +/- 0.8 mumol/L for 5-FU was achieved on the recommended schedule, which compares favorably with conventional IV 5-FU regimens. Among 30 patients assessable for response, there were four complete responses and seven partial responses, and 12 patients with stable disease and seven with progressive disease, reported after 3 months (ie, six cycles) of therapy.

CONCLUSION

A regimen that combines 5-FU and FA has been identified for regional chemotherapy in patients with hepatic metastases from colorectal cancer. The systemic levels of 5-FU achieved are similar to the conventional IV de Gramont regimen using an identical schedule of 5-FU and FA, which implies that this chemotherapy has the best of both worlds, ie, a regional advantage in delivering high drug concentrations to the target organ with adequate systemic cover for extrahepatic micrometastases.
Maximum-tolerated doses of ifosfamide, carboplatin, and etoposide given over 6 days followed by autologous stem-cell rescue: toxicity profile.
Authors: Fields K K , Elfenbein G J , Lazarus H M , Cooper B W , Perkins J B , Creger R J , Ballester O F , Hiemenz J H , Janssen W E , Zorsky P E
Published: February 2017

PURPOSE

A phase I dose-escalation study of ifosfamide, carboplatin, and etoposide (ICE) with autologous stem-cell rescue (ASCR) was conducted to determine the maximum-tolerated dose (MTD) of ICE given over 6 days.

PATIENTS AND METHODS

One hundred fifty-four patients with a variety of poor-prognosis malignancies received escalating doses of ifosfamide 6,000 to 24,000 mg/m2, carboplatin 1,200 to 2,100 mg/m2, and etoposide 1,800 to 3,000 mg/m2 divided over 6 days. Mesna was administered in a dose equal to ifosfamide. ASCR was performed 48 hours after the completion of ICE. The source of stem cells was bone marrow (BM) in patients without BM micrometastases and peripheral-blood stem cells (PBSC) in patients with BM micrometastases. Patients were evaluated for hematologic and nonhematologic toxicities, as well as response to therapy.

RESULTS

The MTD of the ICE regimen is 20,100 mg/m2 of ifosfamide, 1,800 mg/m2 of carboplatin, and 3,000 mg/m2 of etoposide. The dose-limiting toxicities of ICE were CNS toxicity and acute renal failure. Additionally, reversible elevations of serum creatinine levels were noted in 29% of patients treated at the upper dose levels. Forty-six patients were treated at the MTD. Severe, reversible mucositis and enteritis were the major nonhematologic toxicities seen at the MTD (78% and 33%, respectively). The overall mortality rate was 8% for all dose levels (4% at the MTD). At the MTD, the median times to an absolute neutrophil count > or = 0.5 x 10(9)/L, to a platelet count > or = 20 x 10(9)/L, and to discharge were 18, 22, and 24 days, respectively. The overall response rate was 40% for 77 patients with assessable disease at the time of treatment.

CONCLUSION

ICE is well tolerated, with acceptable hematopoietic side effects and predictable organ toxicity.
Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.
Authors: Uderzo C , Valsecchi M G , Bacigalupo A , Meloni G , Messina C , Polchi P , Di Girolamo G , Dini G , Miniero R , Locatelli F
Published: February 2017

PURPOSE

To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized.

PATIENTS AND METHODS

All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors.

RESULTS

In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse).

CONCLUSION

Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.
Localized prostate cancer treated by external-beam radiotherapy alone: serum prostate-specific antigen--driven outcome analysis.
Authors: Lee W R , Hanks G E , Schultheiss T E , Corn B W , Hunt M A
Published: February 2017

PURPOSE

To determine the 5-year rate of survival with no evidence of disease (NED) using strict biochemical criteria in men with prostate cancer treated by external-beam radiotherapy alone and to examine possible clinical and treatment factors that predict the likelihood of NED survival.

MATERIALS AND METHODS

Five hundred men with clinically localized prostate cancer consecutively treated with external-beam radiotherapy alone with no prior, concomitant, or adjuvant endocrine therapy were identified. All patients had serial serum prostate-specific antigen (PSA) values determined after treatment and 451 patients had pretreatment PSA values determined. The median follow-up duration is 20 months (range, 2 to 72; mean, 36).

RESULTS

The 5-year rate of overall survival in this group of patients was 80%. The 5-year rate of survival without clinical evidence of disease (cNED) was 72%. The 5-year rate of survival without evidence of clinical, radiographic, or biochemical relapse (bNED) was 51%. Multivariate analysis demonstrated that a pretreatment serum PSA level < or = 15 ng/mL was the most important predictor of bNED survival (P < .0001). Patients with early-stage (T1, T2a/b) tumors and a pretreatment serum PSA less than 15 ng/mL had a 3-year rate of bNED survival of 86%. The rate of bNED survival for patients with a pretreatment PSA level greater than 15 ng/mL was 38% at 3 years.

CONCLUSION

Pretreatment serum PSA level is the most important predictor of treatment outcome in this group of patients treated with definitive radiotherapy alone. External-beam radiation alone can produce acceptable early rates of bNED survival in patients with clinically organ-confined tumors and a pretreatment PSA level < or = 15 ng/mL. To produce acceptable results in those patients with pretreatment PSA levels more than 15 ng/mL, effective adjuvant treatments in addition to aggressive local treatments are necessary.
Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities.
Authors: Gandara D R , Nahhas W A , Adelson M D , Lichtman S M , Podczaski E S , Yanovich S , Homesley H D , Braly P , Ritch P S , Weisberg S R
Published: February 2017

PURPOSE

Diethyldithiocarbamate (DDTC) blocks cisplatin-induced toxicities in animal models without inhibiting antitumor effects. DDTC chemoprotection was tested in a randomized, multicenter, double-blind comparison versus placebo (PB) in patients with lung or ovarian cancer. Primary end points were nephrotoxicity, ototoxicity, neuropathy, and completion of therapy.

PATIENTS AND METHODS

Between April 1990 and February 1992, 221 patients were registered with small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), or ovarian cancer. Cisplatin (100 mg/m2) and cyclophosphamide (in ovarian cancer) or etoposide (in lung cancer) were administered with either DDTC (1.6 g/m2 over 4 hours) or PB intravenously, every 4 weeks for a planned six cycles.

RESULTS

At an interim safety analysis, data were available for 195 patients from the combined lung and ovarian cancer populations (PB, 99 patients; DDTC, 96 patients). Withdrawal for chemotherapy-induced toxicities occurred in 9% of PB-treated patients and 23% of DDTC-treated patients (P = .008). The mean cisplatin delivered dose-intensity (DDI) was 23 mg/m2/wk on both arms. However, the mean cisplatin cumulative dose delivered (CDD) was 379 mg/m2 on the PB arm, compared with 247 mg/m2 on the DDTC arm (P = .0001). At the time of interim analysis, 28% of PB-treated patients had completed all six cycles of therapy, compared with only 6% of DDTC-treated patients (P < .001). Although, clinical hearing loss, neuropathy, emesis, and myelosuppression were equivalent in the two treatment arms, DDTC-treated patients had more nephrotoxicity as determined by changes in serum creatinine concentration. Toxicities related to DDTC infusion included transient hypertension, flushing, and hyperglycemia. DDTC did not compromise response rates in either tumor type.

CONCLUSION

This study did not demonstrate a significant chemoprotective effect against cisplatin-induced toxicities with the DDTC dose schedule tested. Patients who received DDTC received lower cumulative doses of cisplatin, but were more likely to be withdrawn from treatment early due to chemotherapy-related toxicities.
BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma.
Authors: Mills W , Chopra R , McMillan A , Pearce R , Linch D C , Goldstone A H
Published: February 2017

PURPOSE

To evaluate the outcome of patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy and autologous bone marrow transplantation (ABMT) and to determine the main prognostic factors.

PATIENTS AND METHODS

One hundred seven patients with relapsed or resistant intermediate-/high-grade NHL underwent high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and ABMT at University College Hospitals between September 1981 and February 1993. The minimum follow-up duration of all patients is 6 months.

RESULTS

At 3 months, the overall response rate to BEAM and ABMT was 73% (41% complete response and 32% partial response). The 5-year actuarial overall survival and progression-free survival rates were 41% and 35%, respectively. The early procedure-related mortality rate was 7% (eight of 107 patients). On multivariate analysis, the main prognostic factor was disease status at the time of ABMT. Patients with chemosensitive disease had an actuarial 5-year survival rate of 49% at 5 years compared with 13% for those with chemoresistant disease (P < .001). For patients considered to have chemosensitive disease at the time of transplantation, there is a significant difference in the actuarial progression-free survival rates for those who received high-dose therapy after attaining a partial response to first-line therapy (69% at 5 years) as compared with those with sensitive but relapsed disease (32% at 5 years) (P = .003).

CONCLUSION

Patients with chemosensitive disease benefit most from high-dose chemotherapy, and those who receive such therapy early after achieving a partial response to first-line therapy have a high rate of cure.
Recombinant human interleukin-3 to dose-intensify carboplatin and cyclophosphamide chemotherapy in epithelial ovarian cancer: a phase I trial.
Authors: Veldhuis G J , Willemse P H , van Gameren M M , Aalders J G , Mulder N H , Mull B , Biesma B , de Vries E G
Published: February 2017

PURPOSE

To define the optimal dose of recombinant human interleukin-3 (rhIL-3) required to intensify the dose of carboplatin and cyclophosphamide for advanced epithelial ovarian cancer.

PATIENTS AND METHODS

Seventeen patients were treated on day 1 with carboplatin (dose adjusted for creatinine clearance: range, 257 to 385 mg/m2; median, 300 mg/m2) and cyclophosphamide (750 mg/m2). rhIL-3 5 micrograms/kg/d (n = 10) or 10 micrograms/kg/d (n = 7) was administered subcutaneously (SC) on days 2 through 11. Carboplatin dose was escalated if no postponement of cycles 1 to 3 had occurred.

RESULTS

A 3-week interval was achieved in 62% of cycles and a 4-week interval in 81%, with no difference between the rhIL-3 doses. A neutrophil nadir less than 0.5 x 10(9)/L occurred in 35% of the cycles at 5 micrograms/kg/d and in 52% at 10 micrograms/kg/d of rhIL-3 (nonsignificant difference). The mean platelet nadir in cycle 1 was 173 +/- 78 x 10(9)/L at 5 micrograms/kg/d and 340 +/- 152 x 10(9)/L at 10 micrograms/kg/d of rhIL-3 (P < .05), with a faster recovery of platelets at 10 micrograms/kg/d (P < .05). Progressive myelotoxicity occurred for leukocytes and platelets at both rhIL-3 doses and required chemotherapy postponement in later cycles. The planned six cycles were completed by 41% of patients. Fever (> or = 38.5 degrees C) occurred in 38% of cycles at 5 micrograms/kg/d and in 97% at 10 micrograms/kg/d (P < .0005); headache and myalgias occurred in 30% and 44%, respectively. After two cycles, diffuse erythema, facial edema, and urticaria were observed in two patients at 5 micrograms/kg/d and in five patients at 10 micrograms/kg/d of rhIL-3. This resolved after discontinuation of rhIL-3 and administration of corticosteroids and antihistamines.

CONCLUSION

A dose of 5 micrograms/kg/d of rhIL-3 proved to be optimal to intensify the carboplatin and cyclophosphamide regimen. It permitted the administration of carboplatin and cyclophosphamide combination therapy every 3 weeks in 62% of cycles.
Survey of the provision of supportive care services at National Cancer Institute-designated cancer centers.
Authors: Coluzzi P H , Grant M , Doroshow J H , Rhiner M , Ferrell B , Rivera L
Published: February 2017

PURPOSE

The purpose of this survey was to determine the scope of supportive care services (SCS) designed to promote quality of life during cancer therapies at National Cancer Institute (NCI)-designated cancer centers.

METHODS

A survey was mailed to the medical directors and nursing directors of 52 NCI-designated comprehensive (n = 26), clinical (n = 11), and planning cancer centers (n = 15) in the United States. Only one survey was completed from each institution. Survey questions identified services provided such as pain management, terminal care, psychosocial programs, and spiritual care.

RESULTS

Thirty-nine questionnaires were received for a total response rate of 75%. Of the respondents, 45% were comprehensive cancer centers, 24% clinical cancer centers, and 29% planning centers. One center did not identify their NCI designation. Sixty-one percent of the centers reported research programs in supportive care. Outside funding was reported in 51% of the respondents, with 39% having American Cancer Society (ACS) or National Institutes of Health (NIH) funding and 28% having private industry funding. Overall SCS self-ratings improved from a 21% rating of excellent to very good 5 years ago to the current 54% rating.

CONCLUSION

Survey results provide data on SCS across a representative sample of NCI cancer centers and can be used to develop standards for future cancer control programs.
Patient preferences for treatment of metastatic breast cancer: a study of women with early-stage breast cancer.
Authors: McQuellon R P , Muss H B , Hoffman S L , Russell G , Craven B , Yellen S B
Published: February 2017

PURPOSE

The purpose of this study was to elicit preferences for the treatment of metastatic breast cancer in women with early-stage breast cancer who were given hypothetical treatment scenarios. We predicted that quality of life, demographic, and treatment variables would have an impact on patient preferences.

PATIENTS AND METHODS

One hundred fifteen patients with stage 1-IIIA breast cancer were interviewed. All patients had either mastectomy or lumpectomy plus radiotherapy as primary treatment. Sixty-seven (58%) had prior adjuvant chemotherapy. Patients were given four clinical scenarios that described a woman with metastatic breast cancer who was stated to have a life expectancy of 18 months. Side effects of the treatment options were systematically varied from low (hormonal therapy) to life-threatening (high-dose experimental therapy) and were consistent with common clinical situations. Patients were asked to select which treatment, with its associated toxicity, they would accept and prefer for a 50% chance of specified increments in life expectancy, ie, 5 years, 18 months, 1 year, 6 months, 1 month, and 1 week.

RESULTS

Quality of life at the time of interview, previous chemotherapy treatment, and degree of difficulty of previous treatments did not predict patient preferences. The greater the toxicity potential of the treatment, the less likely patients were to accept the treatment, although approximately 15% of patients would prefer high-risk treatment for as little as 1 month of added life expectancy. Between 34% and 82% of patients would prefer different therapies for a 6-month addition to life expectancy, whereas almost all patients would accept treatment for a 5-year increase in length of survival. Younger patients were more willing to assume the risks of treatment for a small increase in life expectancy. Of note, between 54% and 78% of patients would elect to start the different treatments even without symptoms related to metastatic disease. Moreover, 76% of patients would prefer standard treatment or an experimental agent to reduce symptoms or pain, even if such treatment did not prolong life. Additionally, only 10% of patients would allow randomization to a clinical trial comparing high-dose with standard chemotherapy. Participation in the study was not distressing to most patients.

CONCLUSION

Patients showed clear preferences for specific treatments for metastatic disease when given hypothetical scenarios. There was a wide range of patient preferences for treatment based on risk-benefit assessment, but a substantial percentage of patients would accept the risk of major toxicity for minimal increase in overall survival.
Induction chemotherapy followed by concomitant chemoradiotherapy for advanced head and neck cancer: impact on the natural history of the disease.
Authors: Vokes E E , Kies M , Haraf D J , Mick R , Moran W J , Kozloff M , Mittal B , Pelzer H , Wenig B , Panje W
Published: February 2017

PURPOSE

To determine survival rates and the pattern of failure in head and neck cancer patients treated with induction chemotherapy, limited surgery and concomitant chemoradiotherapy.

PATIENTS AND METHODS

Three cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optional surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concurrent radiation for 5 days (FHX) for a total radiation dose of 65 to 75 Gy. Surgical resection was performed with the intent to spare organ function.

RESULTS

Seventy-one patients were treated at three institutions. Sixty-five patients (91%) had stage IV disease with N2/3 in 46. Thirty-three patients (51%; 95% confidence interval, 39% to 63%) achieved a clinical complete response (CR) to PFL-IFN. Local therapy consisted of surgery in 37 and/or FHX in 55 patients. With a median follow-up duration of 37 months, there have been 20 recurrences (15 local, four distant, and one both local and distant), and 29 deaths, 15 in patients with disease progression and 14 not directly related to the primary tumor. Four patients have developed second malignancies. At 3 years, 69% (+/- 6%) are progression-free and the overall survival rate is 60% (+/- 6%). Toxicity of PFL-IFN included severe or life-threatening mucositis (54%) and myelosuppression (60%). Five patients died of toxicity. During FHX, 70% of patients had grade 3 or 4 mucositis.

CONCLUSION

PFL-IFN is highly active, producing clinical CRs in 51% of patients, and, when followed by FHX, resulting in high local and distant control and overall survival rates. Second malignancies and intercurrent medical disease emerge as major risks to long-term survival. In view of the high toxicity and long treatment duration, further modifications of this approach are required.
Lymphoproliferative disorders after organ transplantation: a report of 24 cases observed in a single center.
Authors: Leblond V , Sutton L , Dorent R , Davi F , Bitker M O , Gabarre J , Charlotte F , Ghoussoub J J , Fourcade C , Fischer A
Published: February 2017

PURPOSE

Organ recipients are at a high risk of post-transplant lymphoproliferative disorders (PTLDs) as a complication of immunosuppressive therapy. We report the incidence, clinical presentation, pathologic findings, treatment, and outcome for 24 cases of PTLD observed at our institution.

PATIENTS AND METHODS

Twenty-four (1.7%) of 1,385 organ transplant recipients developed PTLDs. Dosages of immunosuppressive drugs were reduced in 19 patients. Treatment consisted of anti-B-cell monoclonal antibodies (12 patients), and/or chemotherapy (eight patients), or surgery (two patients).

RESULTS

The median time between grafting and the onset of PTLD was 210 days. Tumors were classified as monomorphic and polymorphic in nine and 15 cases, respectively. Three of 24 cases were of T-cell origin. Genotypic studies confirmed the monoclonality of the tumors in 11 cases among 14 PTLDs tested. Epstein-Barr virus (EBV) infection was associated with 70% of B-cell PTLDs tested. The overall survival duration was 5 months. Ten patients are alive and disease-free with a median follow-up time of 37 months; most were treated with anti-B-cell antibodies. Two other patients died in complete remission of unrelated causes at 33 and 38 months.

CONCLUSION

Anti-B-cell monoclonal antibody therapy seems to be effective in PTLD, even in monoclonal B-cell forms, but other approaches will be necessary to improve survival further.
Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin.
Authors: Gill P S , Espina B M , Muggia F , Cabriales S , Tulpule A , Esplin J A , Liebman H A , Forssen E , Ross M E , Levine A M
Published: February 2017

PURPOSE

Since liposomal encapsulation of anticancer drugs may enhance antitumor activity while reducing toxicity in vitro, we evaluated liposomally encapsulated daunorubucin (DaunoXome; Vestar, Inc, San Dimas, CA) for safety, pharmacokinetics, and potential efficacy in patients with AIDS-related Kaposi's sarcoma (AIDS-KS).

PATIENTS AND METHODS

Forty patients with advanced AIDS-KS were accrued. Successive cohorts received DaunoXome at doses of 10, 20, 30, and 40 mg/m2 given once every 3 weeks, and 40, 50, and 60 mg/m2 given once every 2 weeks. Selected KS and solid-tumor patients underwent pharmacokinetic evaluation.

RESULTS

The area under the plasma concentration curve (AUC) ranged from 16.9 micrograms.h/mL to 375.3 micrograms./mL and the alpha half-life ranged from 7.8 to 8.3 hours at 10 mg/m2 to 60 mg/m2, respectively. Both pharmacokinetic profiles were significantly better compared with free daunorubicin. DaunoXome was well tolerated with no significant alopecia, mucositis, or vomiting. Neutropenia (< 1,000/microL occurred in 17% of cycles and was severe (< 500/microL) in only 2%. Anemia and thrombocytopenia were uncommon. Other adverse events included mild to moderate fatigue, nausea, and diarrhea. Even after cumulative doses greater than 1,000 mg/m2, no significant declines in cardiac function were observed. Twenty-two patients who received 50 and 60 mg/m2 were assessable for tumor response; 12 (55%) had a partial response (PR) or clinical complete response (CR). The median survival duration in all patients was 9 months. Prognostic factors for short survival were low CD4 lymphocyte counts (P = .004) and prior anthracycline therapy (P = .02).

CONCLUSION

DaunoXome has an improved pharmacokinetic profile compared with free daunorubicin, and is well tolerated. DaunoXome can be given safely at doses up to 60 mg/m2 every 2 weeks and has significant antitumor activity in patients with AIDS-KS.
Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.
Authors: Vaughan W P , Kris E , Vose J , Bierman P J , Gwilt P , Armitage J O
Published: February 2017

PURPOSE

A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL).

PATIENTS AND METHODS

Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period.

RESULTS

The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test).

CONCLUSION

High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.