bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I and pharmacologic study of high doses of the topoisomerase I inhibitor topotecan with granulocyte colony-stimulating factor in patients with solid tumors.
Authors: Rowinsky E K , Grochow L B , Sartorius S E , Bowling M K , Kaufmann S H , Peereboom D , Donehower R C
Published: February 2017

PURPOSE

To evaluate the feasibility of escalating doses of the topoisomerase I (topo I) inhibitor topotecan (TPT) with granulocyte colony-stimulating factor (G-CSF) in minimally pretreated adults with solid tumors and to study whether G-CSF scheduling variably affects the ability to escalate TPT doses.

MATERIALS AND METHODS

Thirty-six patients received 121 courses of TPT as a 30-minute infusion daily for 5 days every 3 weeks at doses that ranged from 2.0 to 4.2 mg/m2/d. G-CSF 5 microg/kg/d subcutaneously (SC) was initiated concurrently with TPT (starting on day 1). Because the concurrent administration of TPT and G-CSF resulted in severe myelosuppression at the lowest TPT dose level, an alternate posttreatment G-CSF schedule in which G-CSF dosing began after TPT (starting on day 6) was subsequently evaluated. Plasma sampling was performed to characterize the pharmacologic behavior of high-dose TPT and to determine whether G-CSF altered the pharmacokinetic profile of TPT.

RESULTS

Severe myelosuppression precluded the administration of TPT at the first dose, 2.0 mg/m2/d, with G-CSF on the concurrent schedule. However, dose escalation of TPT with G-CSF on a posttreatment schedule proceeded to 4.2 mg/m2/d. The dose-limiting toxicities (DLTs) were thrombocytopenia and neutropenia. One partial response was noted in a patient with colorectal carcinoma refractory to fluoropyrimidines. Pharmacokinetics were linear within the dosing range of 2.0 to 3.5 mg/m2/d, but TPT clearance was lower at the 4.2-mg/m2/d dose level. At 3.5 mg/m2/d, which is the maximum-tolerated dose (MTD) and recommended dose for subsequent-phase studies of TPT with G-CSF, the area under the concentration-versus-time curves (AUCs) for total TPT and lactone averaged 2.2- and 2.3-fold higher, respectively, than the AUCs achieved at the lowest TPT dose, 2.0 mg/m2/d. The pharmacologic behavior of high-dose TPT was not significantly altered by the scheduling of G-CSF.

CONCLUSION

G-CSF administered after 5 daily 30-minute infusions of TPT permits a 2.3-fold dose escalation of TPT above the MTD in solid-tumor patients, whereas concurrent therapy with G-CSF and TPT results in severe myelosuppression.
Impact of age on outcome of patients with cancer undergoing autologous bone marrow transplant.
Authors: Miller C B , Piantadosi S , Vogelsang G B , Marcellus D C , Grochow L , Kennedy M J , Jones R J
Published: February 2017

PURPOSE

We examined the impact of age on outcomes in patients with cancer undergoing autologous bone marrow transplantation (ABMT).

PATIENTS AND METHODS

All 506 adult patients who underwent ABMT at the Johns Hopkins Oncology Center between January 1987 and January 1994 were studied. A total of 405 patients were aged 18 to 49 years and 101 were aged > or = 50. The effect of age and other prognostic variables on transplant-related mortality (TRM), relapse, and event-free survival rates were analyzed.

RESULTS

Patients aged > or = 50 years has a 2.24-fold increased risk of TRM. Although relapse rates were not different based on age, the increased TRM rate resulted in a slight decrease in overall event-free survival in the older patients. Causes of death were not different by age and were mainly related to preparative regimen toxicity. Length of hospital stay and hospitalization costs were not increased in the older patients.

CONCLUSION

While the TRM rate was higher in older patients, relapse rates were not increased. Nearly 25% of older patients were expected to be cured of the disease. These data support the use of ABMT in eligible older patients, at least up to the age of 65.
Phase II trial of docetaxel in previously untreated advanced non-small-cell lung cancer: a Japanese cooperative study.
Authors: Kunitoh H , Watanabe K , Onoshi T , Furuse K , Niitani H , Taguchi T
Published: February 2017

PURPOSE

This phase II study was conducted to evaluate the efficacy and toxicity of moderate-dose (60 mg/m2) docetaxel in Japanese patients with previously untreated advanced (stage IIIB or IV) non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

Docetaxel 60 mg/m2 was administered intravenously over 1 to 2 hours to patients with previously untreated stage IIIB or IV NSCLC. Treatment was repeated every 3 weeks. No routine premedication was given. The patients' median age was 67 years (range, 40 to 80). Forty-four patients (59%) had adenocarcinoma and 55 (73%) had stage IV disease. The median Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 1.

RESULTS

Seventy-five patients were eligible and treated with docetaxel. Fourteen patients (19%) achieved a partial response (PR); response was not significantly affected by histology or clinical stage. The median survival time for all patients was 297 days. The predominant toxicity was neutropenia, with 87% of patients experiencing grade 3 or 4. Febrile neutropenia was seen in eight patients. Hypersensitivity and edema each occurred in only 4% of patients and were easily manageable. There was no possible treatment-related death of acute exacerbation of pneumonitis.

CONCLUSION

Docetaxel 60 mg/m2 showed significant activity in advanced NSCLC, with a low incidence of hypersensitivity or peripheral edema. Further investigation of this agent in NSCLC is warranted, especially in combination with other active drugs.
Needle aspiration techniques in preoperative selection of patients with thyroid nodules: a long-term study.
Authors: Carpi A , Ferrari E , Toni M G , Sagripanti A , Nicolini A , Di Coscio G
Published: February 2017

PURPOSE

Long-term evaluation of the combination of two needle aspiration techniques (NAT) (fine-needle aspiration [FNA] and aspiration needle biopsy [ANB]) in performing an efficient preoperative selection of palpable thyroid nodules.

PATIENTS AND METHODS

Eight years of extensive use of surgery for the detection of thyroid cancer was compared with 12 years of preoperative selection of by NAT.

RESULTS

A total of 1,140 operations were performed from 1972 to 1979, and 35 malignant nodules were discovered (3.1%). Five thousand four hundred three patients were examined by NAT from 1980 to 1992; 483 (9%) underwent surgery and 158 malignant nodules were excised. The number of malignant nodules identified by NAT was 166 (eight were not excised) (3.1% of the total population examined). The principal clinical and pathologic features were similar in both groups. ANB yielded a definite benign diagnosis in 88 patients with inadequate FNA findings, it correctly identified four malignant nodules diagnosed as benign by FNA, it showed a macrofollicular component in 115 nodules diagnosed by FNA as microfollicular nodules, and it significantly changed the predictive value of 79 suspicions FNA diagnoses.

CONCLUSION

Introduction of NAT reduced the number of operations for palpable thyroid nodules from 143 to 40 per year and increased from four to 13 the number of malignant nodules excised without any change in the overall incidence of malignant nodules. The combination of ANB to FNA significantly contributed to the high and efficient preoperative patient selection, principally by reducing the number of indeterminate or suspicious, as well as false-negative, preoperative FNA diagnoses.
Simultaneous retroperitoneal, thoracic, and cervical resection of postchemotherapy residual masses in patients with metastatic nonseminomatous germ cell tumors of the testis.
Authors: Brenner P C , Herr H W , Morse M J , Sheinfeld J , Aprikian A , Bosl G J , Motzer R J , Bajorin D F , Schantz S , Fair W R , Burt M
Published: February 2017

PURPOSE

We report our experience with simultaneous resection of residual masses above and below the diaphragm in patients with metastatic nomseminomatous germ cell tumor (NSGCT) of the testis.

MATERIALS AND METHODS

Twenty-four patients underwent simultaneous resection of residual postchemotherapy masses in the retroperitoneum and chest, including three who also had radical neck dissection. All had been heavily pretreated with chemotherapy and five had undergone previous retroperitoneal lymph node dissections (RPLNDs).

RESULTS

The combined procedure was performed with no mortality and low morbidity. The median length of the procedure was 5 hours 45 minutes, median blood loss 500 mL, and median length of hospital stay 9 days. Complications included one patient with chylous ascites and one with a prolonged air leak, both of which resolved with conservative management. Eighteen patients had similar pathologic findings in all sites: 13 with necrosis only and five with teratoma only. Six patients had discordant pathology in the abdomen and chest, including one with viable tumor in the chest only and two with viable tumor in the abdomen only. The overall actuarial 5-year survival rate for all patients was 79%.

CONCLUSION

Simultaneous resection of neck, chest, and abdominal residual masses after chemotherapy for germ cell tumors is both a feasible and safe alternative to staged excision in selected patients who require surgical intervention at multiple sites and fulfills the objective of rendering patients disease-free in a single operative procedure.
Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil.
Authors: Fisher B , Dignam J , Mamounas E P , Costantino J P , Wickerham D L , Redmond C , Wolmark N , Dimitrov N V , Bowman D M , Glass A G , Atkins J N , Abramson N , Sutherland C M , Aron B S , Margolese R G
Published: February 2017

PURPOSE

To compare sequential methotrexate (M) and fluorouracil (F) (M-->F) with surgery (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-13) and cyclophosphamide (C), M, and F with M-->F (NSABP B-19), in patients with estrogen receptor (ER)-negative tumors and negative axillary nodes.

PATIENTS AND METHODS

A total of 760 patients were randomized to B-13; 1,095 patients with the same eligibility requirements were randomized to B-19. Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were determined using life-table estimates.

RESULTS

A significant benefit in overall DFS (74% v 59%; P < .001) was demonstrated at 8 years in all B-13 patients who received M-->F (69% v 56% [P = .006] in those or= 50 years). A survival advantage was evident in older patients (89% v 80%; P = .03). In B-19, through 5 years, an overall DFS advantage (82% v 73%; P < .001) and a borderline survival advantage (88% v 85%; P = .06) were evident with CMF. The DFS (84% v 72%; P < .001) and survival (89% v 84%; P = .04) benefits from CMF were greater in women aged F or CMF after lumpectomy and breast irradiation resulted in a low probability of ipsilateral breast tumor recurrence (IBTR). In B-13, the frequency of IBTR was 2.6% following M-->F versus 13.4% in women treated by lumpectomy; it was 0.6% following CMF in B-19. Toxicity >or= grade 3 was more frequent among CMF patients in B-19. The age-related difference in CMF benefit was not related to amount of drug received.

CONCLUSION

M-->F and CMF are effective for node-negative patients with ER-negative tumors. The incidence of local-regional or distant metastases and IBTR decreased after either therapy. The benefit from either therapy was evident in all patients, but the CMF advantage was greater in those F may be used in patients with medical problems that would preclude CMF administration.
Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen.
Authors: Roselli M , Guadagni F , Buonomo O , Belardi A , Vittorini V , Mariani-Costantini R , Greiner J W , Casciani C U , Schlom J
Published: February 2017

PURPOSE

The ability of interferons (IFNs) to enhance tumor-associated antigen expression may be an important approach to enhance the efficacy of some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or therapy. The present study was designed to determine whether systemic IFN alpha-2a administration (via the intramuscular [IM] route) could upregulate the expression of tumor-associated glycoprotein-72 (TAG-72) and/or carcinoembryonic antigen (CEA) at histologically confirmed sites of carcinoma.

PATIENTS AND METHODS

Eighteen patients diagnosed with gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to four dose schedules. In cohorts I and II, patients received two injections of 3 or 6 x 10(6) U IFN alpha-2a per injection, respectively. Patients in cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6) U, respectively, but three injections were given. Tumor and normal colonic mucosa biopsies were obtained from each patient by endoscopy before IFN alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA expression were measured by (1) immunohistochemistry and reported as percent antigen-positive tumor cells, as well as the relative staining intensity, and (2) a quantitative radioimmunoassay.

RESULTS

TAG-72 and CEA levels were consistently increased in tumor biopsies taken from patients in cohorts III and IV. For example, of 10 patients treated in cohorts III and IV, eight had enhanced TAG-72 expression when measured either as percentage TAG-72-positive tumor cells or as an increased MAb staining intensity following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10 patients in cohorts III and IV was also elevated following IFN alpha-2a treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies confirmed higher tumor antigen levels following IFN alpha-2a administration. No such increases in TAG-72 or CEA levels were observed in tumor samples taken from patients in cohorts I and II. CEA or TAG-72 expression in samples of histologically confirmed normal colonic mucosa showed little or no change after IFN alpha-2a treatment.

CONCLUSION

Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA expression at distal tumor sites, which may play an important role in immunodiagnosis and therapy.
International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review.
Authors: Kushner B H , Cheung N K , LaQuaglia M P , Ambros P F , Ambros I M , Bonilla M A , Ladanyi M , Gerald W L
Published: February 2017

PURPOSE

To gain insight into the management of non-metastatic neuroblastoma by examining clinical and biologic features of International Neuroblastoma Staging System (INSS) stage 1 tumors.

METHODS

Patients were staged by both the INSS and the Evans staging system and were evaluated for biologic prognostic factors. Patients with INSS stage 1 received no cytotoxic therapy. The literature was reviewed for clinical and biologic data about INSS stage 1.

RESULTS

We evaluated 10 consecutive patients (median age, 17.5 months) with INSS stage 1; all remain disease-free (median follow-up duration, > 5 years). Tumors were in the abdomen (n = 6), chest (n = 3), or pelvis (n = 1). Neuroblastoma involved margins of resection in six tumors. Poor-prognostic biologic findings included tumor-cell diploidy (n = 2) and unfavorable Shimada histopathology (n = 2). Two patients were to receive chemotherapy for, respectively, a tumor deemed unresectable and a tumor classified as Evans stage III; second opinions resulted in surgical management alone in each case. Published reports confirm that some INSS stage 1 patients (1) are at risk for overtreatment, and (2) have poor-prognostic biologic findings yet do well.

CONCLUSION

Surgery alone suffices for INSS stage 1 neuroblastoma, even if biologic prognostic factors are unfavorable, microscopic disease remains after surgery, and tumor size is suggestive of "advanced-stage" status in other staging systems. Attempts to resect regionally confined neuroblastomas should take precedence over immediate use of cytotoxic therapy; otherwise, some patients may receive chemotherapy or radiotherapy unnecessarily.
Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.
Authors: Sculier J P , Paesmans M , Bureau G , Giner V , Lecomte J , Michel J , Berchier M C , Van Cutsem O , Küstner U , Kroll F , Sergysels R , Mommen P , Klastersky J
Published: February 2017

PURPOSE AND METHODS

The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin).

RESULTS

Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival.

CONCLUSION

We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.
Radiation in management of patients with dermatofibrosarcoma protuberans.
Authors: Suit H , Spiro I , Mankin H J , Efird J , Rosenberg A E
Published: February 2017

PURPOSE

The preferred treatment of dermatofibrosarcoma protuberans (DFSP) is wide resection, namely, margins > or = 3 cm beyond the evident disease and histologically negative margins. We assess the success achieved by radiation combined with surgery for positive/close margins or by radiation alone for those tumors that are not resectable for technical/medical reasons. The literature on this point is virtually nonexistent.

MATERIALS AND METHODS

The outcome of treatment of 18 patients with DFSP by radiation alone (n = 3) and radiation and surgery (n = 15) at the Massachusetts General Hospital was assessed. All of the lesions at the time of the treatment by radiation alone or combined with surgery were less than 10 cm. This was the maximum dimension. The actual tumor volume was much less than indicated by this maximum dimension, as the tumors were usually relatively flat.

RESULTS

The 10-year actuarial local control rate was determined to be 88%. Local control was realized in the three patients treated by radiation alone, with follow-up periods of > or = 9 years. Among 15 patients treated by radiation and surgery, there have been three local failures; the 10-year actuarial local control rate was 84%. The three local failures occurred in 12 patients whose surgical margins were positive. One of these three local failures developed in the group of two patients whose lesions were scored as grade II.

CONCLUSION

Radiation in well-tolerated dose schedules is an effective option in the management of patients with DFSP. This appears to be true for radiation alone or postoperatively for margin-positive disease (primary or recurrent).
Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer.
Authors: Fennelly D , Aghajanian C , Shapiro F , O'Flaherty C , McKenzie M , O'Connor C , Tong W , Norton L , Spriggs D
Published: February 2017

PURPOSE

Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy. All patients received standard premedication.

PATIENTS AND METHODS

Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24).

RESULTS

A total of 194 cycles of therapy were administered, with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen. Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity was 90.75% of that planned and greater than two fold the standard dose-intensity. Partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting toxicity was reached at 100 mg/m2 with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group of heavily pretreated patients on this weekly schedule.

CONCLUSION

(1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.
Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck: results of the Yale Mitomycin Randomized Trials.
Authors: Haffty B G , Son Y H , Papac R , Sasaki C T , Weissberg J B , Fischer D , Rockwell S , Sartorelli A C , Fischer J J
Published: February 2017

PURPOSE

Two consecutive randomized trials were run at our institution using the bioreductive alkylating agent mitomycin as an adjunct to radiation therapy in an effort to improve outcome in patients with squamous cell carcinoma of the head and neck.

METHODS

Between 1980 and 1992, two consecutive randomized trials using mitomycin (trial 1) and mitomycin with dicumarol (trial 2) as an adjunct to radiation therapy in patients with squamous cell carcinoma of the head and neck were conducted at our institution. The patients were stratified by intent of therapy, extent of disease, and primary tumor site. Within each strata, patients were randomized to receive radiation therapy with or without mitomycin (trial 1) or mitomycin/dicumarol (trial 2).

RESULTS

A total of 203 patients were enrolled onto both trials, 195 of whom were eligible for analysis. Patients were equally balanced with respect to sex, age, extent of disease, primary site, radiation dose, and total duration of radiation treatment. Hematologic toxicities were more frequently noted in the drug-treated arms, but were acceptable with no drug-related treatment deaths. Nonhematologic toxicities were acceptable and not significantly different between the two arms. As of September 1995, with a median follow-up of 138 months, a statistically significant benefit occurred in the mitomycin arms with respect to cause-specific survival (0.74 +/- 0.05 v 0.51 +/- 0.05; P = .005), local recurrence-free survival (0.85 +/- 0.04 v 0.66 +/- 0.05; P = .002), and local regional recurrence-free survival (0.76 +/- 0.05 v 0.54 +/- 0.05; P = .003). No statistically significant difference in overall survival was obtained (0.48 +/- 0.05 mitomycin arms v 0.42 +/- 0.05 radiation alone).

CONCLUSION

The bioreductive alkylating agent mitomycin is a safe and effective adjunct to radiation therapy in the treatment of squamous cell carcinoma of the head and neck. The statistically and clinically significant improvement in local regional relapse and cause-specific survival obtained support the use of mitomycin as an adjunct to radiation therapy in the management of squamous cell carcinoma of the head and neck.
Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion.
Authors: Edwards R P , Gooding W , Lembersky B C , Colonello K , Hammond R , Paradise C , Kowal C D , Kunschner A J , Baldisseri M , Kirkwood J M , Herberman R B
Published: February 2017

PURPOSE

To compare the toxicity, pharmacokinetics, and efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (I.P.) interleukin-2 (IL-2) by two different infusion schedules.

PATIENTS AND METHODS

Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m2/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy. Eligibility criteria included > or = six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer.

RESULTS

Forty-one eligible patients received I.P. IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m2 as the maximum-tolerated dose (MTD), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established. Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35). The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%. For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months).

CONCLUSION

I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.
Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival.
Authors: Wood D P , Banerjee M
Published: February 2017

PURPOSE

To determine whether the presence of circulating prostate cells in the bone marrow is associated with disease-free survival in patients undergoing radical prostatectomy.

MATERIALS AND METHODS

We evaluated the bone marrow of 86 patients with clinically localized prostate cancer treated by radical prostatectomy for the presence of circulating prostate cells using reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of prostate-specific antigen (PSA) mRNA. Follow-up duration ranged from 1 to 43 months (mean, 15.4).

RESULTS

Two of 47 patients (4%) with negative RT-PCR PSA results and 10 of 39 patients (26%) with positive RT-PCR PSA results have had disease recurrence. Patients whose RT-PCR PSA results were positive had a significantly shorter disease-free survival period than those patients with negative RT-PCR PSA results (P = .004). RT-PCR status correlated significantly with serum PSA level (P = .001) and pathologic stage (P = .003). Based on Cox's proportional hazards models, RT-PCR status was found to be a significant predictor of disease-free survival. However, after controlling for PSA level, RT-PCR status was not significant in predicting disease-free survival.

CONCLUSION

RT-PCR PSA of bone marrow may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Currently, this test should not be used to determine if patients receive definitive local therapy.
Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit.
Authors: McQuaker I G , Hunter A E , Pacey S , Haynes A P , Iqbal A , Russell N H
Published: February 2017

PURPOSE

To assess the clinical and economic benefit of low-dose (50 microg/m2) filgrastim after peripheral blood stem-cell transplantation (PBSCT) in a randomized, placebo-controlled double-blinded study.

PATIENTS AND METHODS

Thirty-eight patients with lymphoproliferative disorders were randomized to receive low-dose filgrastim (19 patients) or placebo (19 patients) beginning on the first day after stem-cell reinfusion and continuing until absolute neutrophil count (ANC) was greater than 0.5 x 10(9)/L. All patients received greater than 2.5 x 10(6) CD34+ cells/kg, which was mobilized with chemotherapy and filgrastim 300 microg from the fifth day. An economic analysis was performed based on the outcome in the two groups.

RESULTS

Neutrophil engraftment was significantly more rapid in patients who received filgrastim with a median number of days until ANC was greater that 0.5 x 10(9)/L of 10 (9 to 13) versus 14 (9 to 19; P < .0001). The time to reach an ANC greater than 1 x 109/L was 12 (9 to 14) versus 16 days (10 to 25; P < .0001). The total number of patients who required intravenous antibiotic therapy was lower in the filgrastim-treated group (68%) compared with the placebo group (89%); also, the median number of days with fever and the duration of antibiotic therapy were shorter, although these differences did not reach statistical significance. However, although only three of 19 (16%) patients who received filgrastim required amphotericin, 11 of 19 (58%) who received placebo did require it, and amphotericin usage was significantly less in the filgrastim group (P = .029). Finally, in-patient stay was significantly shortened in those who received filgrastim from 16 (13 to 23) to 13 days (11 to 18; P = .0003).

CONCLUSION

Low-dose filgrastim significantly reduces neutrophil engraftment time post-PBSCT and also reduces in-patient stay and costs, which makes it economically viable for patients who are undergoing high-dose chemotherapy.
Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD.
Authors: Bonfante V , Santoro A , Viviani S , Devizzi L , Balzarotti M , Soncini F , Zanini M , Valagussa P , Bonadonna G
Published: February 2017

PURPOSE

This study analyzed long-term results in patients with Hodgkin's disease who were resistant to or relapsed after first-line treatment with MOPP and ABVD. Response to salvage treatments and prognostic factors were also evaluated.

PATIENTS AND METHODS

The study population included 115 refractory or relapsed patients among a total of 415 patients treated with alternating or hybrid MOPP-ABVD followed by radiotherapy (25 to 30 Gy) to initial bulky sites. The median follow-up duration of the present series was 91 months. Thirty-nine of 115 patients (34%) showed disease progression while on primary treatment (induction failures); 48 relapsed after complete remissions that lasted < or = 12 months and 28 after complete remission that lasted more than 12 months from the end of all treatments.

RESULTS

At 8 years, the overall survival rate was 27%, being 54% and 28% in patients whose initial complete remission was longer or shorter than 12 months, respectively, and 8% in induction failures (P < .001). Response to first-line chemotherapy and disease extent at first progression significantly influenced long-term results, as well as the incidence and duration of complete remission.

CONCLUSION

The present data confirm previous observations that showed the main prognostic factors to influence outcome after salvage treatment are response duration to first-line therapy and disease extent at relapse. The results indicate that patients who relapse after the alternating MOPP/ABVD regimen have a prognosis similar to that of patients who relapse after a four-drug regimen (MOPP or ABVD alone). Re-treatment with initial chemotherapy seems the treatment of choice for patients who relapse after an initial complete remission that lasts greater than 12 months, while the real impact of high-dose chemotherapy or new regimens should be assessed in resistant patients.
Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31.
Authors: Pilepich M V , Caplan R , Byhardt R W , Lawton C A , Gallagher M J , Mesic J B , Hanks G E , Coughlin C T , Porter A , Shipley W U , Grignon D
Published: February 2017

PURPOSE

Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated.

MATERIALS AND METHODS

In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm.

RESULTS

Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03).

CONCLUSION

Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.
Markers of radioresistance in squamous cell carcinomas of the head and neck: a clinicopathologic and immunohistochemical study.
Authors: Raybaud-Diogène H , Fortin A , Morency R , Roy J , Monteil R A , Têtu B
Published: February 2017

PURPOSE

The lack of accurate criteria to predict the response to radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HN-SCC) remains a major problem. The purpose of this study was to investigate the role of several biologic tumor markers to complement clinical prognostic factors in the assessment of response to radiotherapy in SCCs.

PATIENTS AND METHODS

p53, ki-67, c-erb B-2, heat-shock protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated by immunohistochemistry on biopsies from 101 patients treated for head and neck cancer by radical radiotherapy. Expression of each marker was correlated with local control and survival using Kaplan-Meier curves. A Cox regression multivariate analysis was also performed that included all clinical and immunohistochemical variables.

RESULTS

Expression of p53 and low cell proliferation allowed identification of patients whose tumors did not respond to radiation. Patients with p53-expressing tumors displayed a relative risk (RR) of 3.78 for not being controlled by radiotherapy compared with patients with p53-negative tumors. For tumors with a high growth fraction (ki-67 > 20%) the RR was 0.25 compared with tumors with a low growth fraction (ki-67 < 20%). When p53 expression and cell proliferation were considered simultaneously in a Cox model, the association with resistance to radiation was significant (P = .000004). The RR for resistance with one (p53 staining or ki-67 < 20%) or two (p53 staining and ki-67 < 20%) unfavorable markers was, respectively, 3.8 and 14.87.

CONCLUSION

Patients whose tumor expressed p53 with low growth fraction (ki-67 < 20%) had a strong probability not to respond to radiation therapy. Similarly, absence of p53 expression with a high cell proliferation predicted an excellent outcome after radiotherapy even for patients with advanced disease. Prediction of the outcome of radiotherapy would eventually facilitate the early choice of an adequate treatment.
Placebo-controlled trial of sucralfate for inhibiting radiation-induced esophagitis.
Authors: McGinnis W L , Loprinzi C L , Buskirk S J , Sloan J A , Drummond R G , Frank A R , Shanahan T G , Kahanic S P , Moore R L , Schild S E , Humphrey S L
Published: February 2017

PURPOSE

To determine whether a sucralfate oral solution can prevent/alleviate radiation-induced esophagitis.

PATIENTS AND METHODS

Patients included on this clinical trial were beginning thoracic radiation therapy to the mediastinum. Following stratification, they were randomized, in a double-blind manner, to receive a sucralfate solution or an identical-appearing placebo solution. Esophagitis was measured by physicians who used standard criteria and also by patients who used short questionnaires completed weekly during the course of the trial.

RESULTS

A total of 97 assessable patients were entered onto this clinical trial. During the first 2 weeks of the study, two placebo patients (4%) stopped their study medication, compared with 20 sucralfate patients (40%). This was related to substantially increased incidences of gastrointestinal toxicity (58% of sucralfate patients v 14% of placebo patients; P > .0001). There was no substantial benefit from the sucralfate in terms of esophagitis scores.

CONCLUSION

This oral sucralfate solution does not appear to inhibit radiation-induced esophagitis and is associated with disagreeable gastrointestinal side effects in this patient population.
Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer.
Authors: Masters G A , Hoffman P C , Hsieh A , Drinkard L C , Mick R , Samuels B L , Guaspari A , Golomb H M , Vokes E E
Published: February 2017

PURPOSE

We designed a phase I dose-escalation study of vinorelbine on a novel (daily-times-three) schedule with ifosfamide with granulocyte colony-stimulating factor (G-CSF) support to define the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of vinorelbine in this combination.

PATIENTS AND METHODS

Cohorts of patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received vinorelbine starting at 15 mg/m2 on days 1, 2, and 3, and ifosfamide starting at 2.0 g/m2 on days 1, 2, and 3 with G-CSF support for all patients. Cycles were repeated every 21 days. Plasma vinorelbine concentrations were also analyzed.

RESULTS

Forty-two patients were treated. The median age was 58 years (range, 34 to 75) and 41 had a performance status of 0 or 1. The DLT was neutropenia and sepsis at a maximum-administered vinorelbine dose of 35 mg/m2 for 3 days. The recommended phase II dose was vinorelbine 30 mg/m2 with ifosfamide 1.6 g/m2 both given on 3 consecutive days. The overall response rate was 40% (17 of 42; all partial responders). The median survival duration was 50 weeks, with a 1-year survival rate of 48%. Pharmacokinetic analysis showed that vinorelbine in this combination and on this schedule is cleared 1.5 to two times faster than in single-agent once-weekly studies.

CONCLUSION

Myelosuppression is the DLT of this regimen with no major subjective toxicities. With tolerable toxicity and an encouraging 1-year survival rate of 48%, further investigation of this new vinorelbine schedule is warranted in this and other combination regimens.
Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors.
Authors: Klempnauer J , Ridder G J , von Wasielewski R , Werner M , Weimann A , Pichlmayr R
Published: February 2017

PURPOSE

To define the prognostic factors after surgical resection of bile duct carcinomas at the hepatic bifurcation.

PATIENTS AND METHODS

The retrospective single-center experience details 151 patients after surgical resection of central bile duct carcinoma performed between 1971 and 1995. Tumor removal was accomplished by resection of the bile duct bifurcation either alone (group I, n = 33), in combination with hepatic resection (group II, n = 77), or combined with hepatic and vascular resection (group III, n = 41). Survival analysis was performed by the Kaplan-Meier method and the relationship between each of the clinicopathologic variables and survival was assessed by the log-rank test. Multivariate results were confirmed using Cox regression.

RESULTS

The overall hospital mortality rate was 9.9% and depended on the extent of resection (group 1, 6.1%; group II, 7.8%; group III, 17.1%). After exclusion of hospital deaths, the overall patient survival rate was 28.4% at 5 and 15.5% at 10 years, with a median survival duration of 2.05 +/- 0.23 years. Univariate survival analysis identified tumor size, lymph node metastases, residual tumor stage, and tumor grading as factors with a statistically significant prognostic impact. Survival prognosis was not influenced by the site of the tumor according to the classification of Bismuth and Corlette, extent of resection, International Union Against Cancer (UICC) stage, perineural and vascular invasion, age, or sex. In a multivariate Cox analysis, only lymph node metastases and residual tumor stage proved to be of independent prognostic significance.

CONCLUSION

Resection of central bile duct carcinoma is feasible in many patients and a favorable outcome after resection is mainly determined by curative resection and the absence of lymph node metastases.
Surgical second look in ovarian cancer: a randomized study in patients with laparoscopic complete remission--a Northeastern Oncology Cooperative Group-Ovarian Cancer Cooperative Group Study.
Authors: Nicoletto M O , Tumolo S , Talamini R , Salvagno L , Franceschi S , Visonà E , Marin G , Angelini F , Brigato G , Scarabelli C , Carbone A , Cecchetto A , Prosperi A , Rosabian A , Giusto M , Cima G P , Morassut S , Nascimben O , Vinante O , Fiorentino M V
Published: February 2017

PURPOSE

The usefulness of extensive and repetitive surgery for patients with ovarian cancer still remains unproven (at least for some conditions). We planned an accurate prospective test of the hypothesis that patients with advanced-stage disease, after they had reached a clinical complete remission (CR), may benefit from surgical second look (SSL).

PATIENTS AND METHODS

One hundred two patients in CR (as assessed by clinical findings, markers, and visualization by computed tomographic [CT] scan and laparoscopy), after initial debulking and first-line chemotherapy, were randomized to two arms, which were well balanced for predictive criteria such as age, stage at presentation, histology, grading, date of randomization, and residua after first surgery. Forty-eight patients were randomly assigned to receive follow-up evaluation only, while 54 were assigned to receive second surgery (eight of them refused). Of 46 surgical patients, 35 had negative and 11 positive surgical findings (24% clinically false-negative).

RESULTS

Despite the microscopic residua found at open surgery, and the fact that the patients were then treated with second-line chemotherapy, SSL did not increase the probability of survival in this setting. In an analysis of the results according to the intention-to-treat criteria, after a 60-month follow-up period, the overall survival rates in the two groups of patients (SSL v no SSL) were 65% and 78%, respectively (P = .14). Multivariate analysis according to predictive criteria confirmed there was no significant difference between the two groups (P = .39).

CONCLUSION

Our study shows the following: (1) our second-line treatment is scarcely effective; (2) SSL accurately defines complete responders to first-line chemotherapy; (3) SSL per se does not prolong survival; and (4) if confirmed, a less invasive procedure could replace SSL as a valuable method in new first-line regimens in ovarian cancer patients with clinical CR confirmed by laparoscopy.
Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: the basis for an adjuvant therapy trial.
Authors: D'Amico A V , Whittington R , Malkowicz S B , Schultz D , Tomaszewski J E , Wein A
Published: February 2017

PURPOSE

A multivariable analysis to evaluate the potential clinical and pathologic factors that predict for early biochemical failure in patients with pathologically organ-confined and margin-negative disease was performed to define patients who may benefit from adjuvant therapy.

PATIENTS AND METHODS

Three hundred forty-one prostate cancer patients treated with a radical retropubic prostatectomy between January 1989 and June 1995 and found to have pathologically organ-confined and margin-negative disease comprised the study population. A logistic regression multivariable analysis to evaluate the predictive value of the preoperative prostate-specific antigen (PSA) level, pathologic (prostatectomy) Gleason score, and pathologic stage on PSA failure occurring during the first postoperative year was performed.

RESULTS

Predictors of PSA failure during the first postoperative year in patients with pathologically organ-confined disease included pathologic Gleason score > or = 7 (P = .0007) and preoperative PSA level greater than 10 (P < .0001). Corresponding 3-year freedom-from-PSA-failure rates for these pathologic organ-confined patients with both, one, or neither of these factors were 60%, 75% to 84%, and 95%, respectively (P < .0001).

CONCLUSION

Prostate cancer patients with pathologically organ-confined and margin-negative disease and a preoperative PSA level greater than 10 ng/mL or a pathologic Gleason score > or = 7 have significant decrements in short-term PSA-failure-free survival. Therefore, these patients should be considered for adjuvant therapy in the setting of a phase III clinical trial.