bluuebunny/crossref_metadata_2025 huggingface dataset:
Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy‐proven Stage IIIA(N2) nonsmall cell lung carcinoma
Authors: De Marinis Filippo , Nelli Fabrizio , Migliorino Maria Rita , Martelli Olga , Cortesi Enrico , Treggiari Stefano , Portalone Luigi , Crispino Carlo , Brancaccio Luigi , Gridelli Cesare
Published: October 2003

BACKGROUND

The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC).

METHODS

Forty‐nine chemotherapy‐naïve patients (median age, 61 years; World Health Organization performance status, 0–1) with biopsy‐proven Stage IIIA(N2) disease received 1000 mg/m2 gemcitabine, 125 mg/m2 paclitaxel, and 50 mg/m2 cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy.

RESULTS

Grade 3–4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3–4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty‐six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1‐year survival rate of 85%.

CONCLUSIONS

GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11662
Cutaneous angiosarcoma of the scalp
Authors: Pawlik Timothy M. , Paulino Augusto F. , Mcginn Cornelius J. , Baker Laurence H. , Cohen Deborah S. , Morris Jeffery S. , Rees Riley , Sondak Vernon K.
Published: October 2003

BACKGROUND

Angiosarcoma is a malignant tumor of vascular endothelial cells that arises in the head and neck. It is a rare, difficult to treat, and lethal tumor.

METHODS

Clinical data from patients who were diagnosed with angiosarcoma of the scalp between 1975 and 2002 at the University of Michigan were reviewed. Analysis was performed to assess for factors impacting time to recurrence and survival.

RESULTS

The study was comprised of 29 patients with a median age of 71.0 years. Most patients presented after a delay in diagnosis with either a bruise‐like macule (48.3%) or a nonbruise‐like nodule (51.7%). Seventy‐five percent of patients had pathologic Stage T2 disease, and 76% of patients had high‐grade tumors. Virtually all patients underwent surgical excision (96.6%); however, negative surgical margins were achieved in only 21.4% of patients. Multiple lesions on presentation were associated with a shorter time to recurrence (P = 0.02). The median actuarial survival was 28.4 months. Younger patients and patients with Stage T1 disease had improved survival (P = 0.024 and P = 0.013, respectively). Radiation therapy was associated significantly with a decreased chance of death (hazard ratio, 0.16; P = 0.006).

CONCLUSIONS

Although surgery remains the first option for the treatment of patients with angiosarcoma of the scalp, achieving negative margins often is impossible. Patients who are younger and who have less extensive disease fare better. Postoperative radiation therapy should be employed routinely, as it may lead to improved survival. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11667
Relation between the method of detection of initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma
Authors: Chen Changhu , Orel Susan G. , Harris Eleanor E. R. , Hwang Wei‐Ting , Solin Lawrence J.
Published: October 2003

BACKGROUND

Mammography and physical examination are routine methods for the detection of ipsilateral local recurrence and contralateral breast carcinoma in patients initially undergoing breast conservation treatment. The current study reports the relation between the method of detection of the initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma.

METHODS

A retrospective review was performed of the records of female patients with initial American Joint Committee on Cancer (AJCC) Stage I and II invasive breast carcinoma who developed ipsilateral local recurrence or contralateral breast carcinoma after breast conservation treatment. The method of detection of local recurrence in the ipsilateral breast and the method of detection of contralateral breast carcinoma were compared with the method of detection of the primary tumor.

RESULTS

There were 125 ipsilateral breast local recurrences and 71 contralateral breast carcinoma cases detected. Of the 125 recurrences in the ipsilateral breast, 38% (48 recurrences) were detected by mammography only, 37% (46 recurrences) were detected by physical examination only, and 25% (31 recurrences) were detected by both methods. Of the 71 contralateral breast carcinoma cases, 53% (38 cases) were detected by mammography only, 23% (16 cases) were detected by physical examination only, and 24% (17 cases) were detected by both methods. When the primary tumors were detected by mammography only, 21% of the local recurrences (3 of 14 local recurrences) and 19% of the contralateral breast carcinoma cases (4 of 21 cases) were detected by physical examination only. When the primary tumors were detected by physical examination only, 24% of the local recurrences (14 of 58 local recurrences) and 42% of the contralateral breast carcinoma cases (8 of 19 cases) were detected by mammography only. When stratified by the interval between diagnosis of the primary tumor and ipsilateral local recurrence or contralateral breast carcinoma (≤ 5 years vs. > 5 years) or age of the patient at the time of ipsilateral breast recurrence or contralateral breast carcinoma (age ≤ 49 years vs. age ≥ 50 years), both breast examination and mammography were found to be important in the detection of locally recurrent tumor and contralateral breast carcinoma in each subgroup of the patients, regardless of the method of presentation of the primary tumor.

CONCLUSIONS

Both mammography and physical examination were found to be significant in the detection of locally recurrent tumor in the ipsilateral breast and in the detection of contralateral breast carcinoma, regardless of the method of detection of the primary tumor. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11685
Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen‐independent prostate carcinoma
Authors: Hellerstedt Beth , Pienta Kenneth J. , Redman Bruce G. , Esper Peg , Dunn Rodney , Fardig Judith , Olson Karin , Smith David C.
Published: October 2003

BACKGROUND

The authors evaluated the combination of oral cyclophosphamide, oral prednisone, and diethylstilbestrol (DES) in patients with androgen‐independent prostate carcinoma (AIPC).

METHODS

Thirty‐seven patients with prostate carcinoma refractory to androgen ablation who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled in the current study. They were treated with oral cyclophosphamide 100 mg per day on Days 1–20, prednisone 10 mg per day continuously, and DES 1 mg continuously, on a 30‐day cycle. Warfarin 1 mg per day was given as prophylaxis for thrombosis. Patient levels of prostate‐specific antigen (PSA) were monitored on a monthly basis, with imaging studies every 3 months. Patients continued to receive therapy until disease progression or the occurrence of significant toxicity. The effect of therapy on the patient's quality of life was assessed using the Functional Assessment of Cancer Therapy–Prostate.

RESULTS

Thirty‐six patients were evaluable for response. Of the 36 patients, 15 (42%) had a 50% or greater decline in PSA levels from pretreatment levels and 1 patient (6%) with measurable disease had a partial response to therapy. The median duration of response was 4.5 months (range, 4–18 months). The overall median survival period was 16.4 months. The treatment was well tolerated, with only three patients removed from the study for toxicities associated with treatment. One patient, who had been treated for more than 24 months, developed acute leukemia. Quality of life evaluation in 17 patients showed a significant improvement in responders, whereas nonresponders had no deterioration while receiving therapy.

CONCLUSIONS

Cyclophosphamide, prednisone, and DES represent a well tolerated, low‐cost combination therapy with significant activity in the treatment of patients with AIPC. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11686
Weekly administration of docetaxel for symptomatic metastatic hormone‐refractory prostate carcinoma
Authors: Gravis Gwenaelle , Bladou Franck , Salem Naji , Macquart‐Moulin Geneviève , Serment Gérard , Camerlo Jacques , Genre Dominique , Bardou Valérie‐Jeanne , Maraninchi Dominique , Viens Patrice
Published: October 2003

BACKGROUND

The current Phase II study investigated the clinical benefit, impact on quality of life (QOL), and tolerability of weekly docetaxel in symptomatic patients with metastatic hormone‐refractory prostate carcinoma (HRPC).

METHODS

Patients received weekly docetaxel 35 mg/m2 intravenously for 6 consecutive weeks followed by a 2‐week rest repeatedly for a maximum of 24 weeks of treatment. Clinical benefit evaluations, based on Karnofsky performance status (KPS) and pain, were assessed weekly during therapy. A clinical benefit response was defined as a sustained (≥ 4‐week) improvement in at least one of these parameters without worsening in the other. Patient‐assessed QOL (using the European Organization for Research and Treatment of Cancer QLQ‐C30), changes in prostate‐specific antigen (PSA) levels, tumoral response, and toxicity also were evaluated.

RESULTS

Thirty men (median age, 67 years), 15 of whom had received previous chemotherapy, were treated. Overall, 46% of patients achieved a positive pain response and 48% achieved a 50%‐or‐greater reduction in PSA. KPS was high at baseline (80%), and no significant changes in this parameter were observed. Compared with baseline, all scores improved after the first cycle of therapy, particularly emotional (P = 0.015), pain (P = 0.001), constipation (P = 0.001), and global QOL (P = 0.011) scores. After the second cycle, dyspnea scores decreased (P = 0.010). At the last QOL assessment, there also was deterioration in terms of fatigue (P = 0.013), dyspnea (P = 0.010), and physical functioning (P = 0.017). Toxicity was mild and included neutropenia (Grade 3–4, n = 2).

CONCLUSIONS

Of these elderly symptomatic patients with HRPC, half had received previous chemotherapy. Weekly docetaxel was found to be associated with improvements in clinical benefit response and in QOL and was well tolerated. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11687
Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1‐related breast carcinoma
Authors: Foulkes William D. , Metcalfe Kelly , Hanna Wedad , Lynch Henry T. , Ghadirian Parviz , Tung Nadine , Olopade Olofunmilayo , Weber Barbara , McLennan Jane , Olivotto Ivo A. , Sun Ping , Chappuis Pierre O. , Bégin Louis R. , Brunet Jean‐Sébastien , Narod Steven A.
Published: October 2003

BACKGROUND

A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1‐related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1‐related breast carcinomas.

METHODS

The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size.

RESULTS

A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20).

CONCLUSIONS

The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1‐related breast carcinoma. Cancer 2003. ©2003 American Cancer Society.

DOI 10.1002/cncr.11688
Application of immunofluorescence for intraoperative evaluation of sentinel lymph nodes in patients with breast carcinoma
Authors: Munakata Satoru , Aihara Tomohiko , Morino Hideo , Takatsuka Yuichi
Published: October 2003

BACKGROUND

Sentinel lymph node (SLN) sampling is used to predict axillary lymph node (AxLN) metastasis in patients with breast carcinoma; AxLN sampling can be avoided in SLN‐negative patients. Multistep sectioning and immunohistochemistry are reported to increase the sensitivity of micrometastasis detection. The authors used immunofluorescence (IF) staining with cytokeratin (CK) antibodies for intraoperative evaluation of touch imprints from multistep sections of SLNs.

METHODS

A combined total of 150 SLNs from 69 patients who had breast carcinoma and underwent surgery were analyzed. SLNs were sectioned at 2 mm intervals, and touch imprints subsequently were prepared. After ethanol fixation, slides were incubated with fluorescein isothiocyanate–conjugated CK and propidium iodide and then subjected to microwave irradiation for 3 minutes. Finally, fluorescence microscopy was used to evaluate slides for the presence or absence of metastatic disease.

RESULTS

Metastatic disease was identified in 36 (24.0%), 26 (17.3%), 32 (21.3%), and 31 (20.7%) of 150 lymph nodes using IF staining, Papanicolaou (Pap) staining, immunocytochemical (ICC) staining, and hematoxylin and eosin (H & E) staining, respectively. The sensitivities of IF, Pap, ICC, and H & E staining were 94.6%, 70.3%, 86.5%, and 83.8%, respectively. Except for IF staining (specificity, 99.1%), each method had a specificity of 100%. The accuracy rates for IF, Pap, ICC, and H & E staining were 98.0%, 92.7%, 96.7%, and 96.0%, respectively.

CONCLUSIONS

IF is a rapid, highly sensitive, and highly specific staining technique by which touch imprints can be used to intraoperatively evaluate SLNs in patients with breast carcinoma. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11689
Phase II evaluation of three‐day topotecan in recurrent platinum‐sensitive ovarian carcinoma
Authors: Miller David Scott , Blessing John A. , Lentz Samuel S. , McMeekin D. Scott
Published: October 2003

BACKGROUND

Topotecan, administeredintravenously at a dose of 1.5 mg/m2 per day for 5 days every 21 days, is an established regimen in the treatment of recurrent ovarian carcinoma. Alternate dosing strategies have sought to improve toxicity. The authors evaluated the tolerability and antitumor activity of a 3‐day topotecan regimen.

METHODS

A multicenter Phase II study, which included patients with platinum‐sensitive ovarian carcinoma, was conducted. Patients were to receive an intravenous dose of topotecan of 2.0 mg/m2 per day for 3 days every 21 days until disease progression or unacceptable toxicity occurred. Doses were modified in 0.25‐mg/m2 increments based on tolerability. Granulocyte–colony‐stimulating factor support was used as necessary.

RESULTS

From February to June 2000, 30 patients were enrolled. Their median age was 56 years (range, 41–81 years). Twenty‐nine patients were evaluable for toxicity and efficacy. A median of 5 courses (range, 1–11 courses) of topotecan was administered. Eighteen of 30 (60%) patients experienced Grade 4 neutropenia. There was one report each of Grade 4 thrombocytopenia, anemia, and gastrointestinal toxicity (grading performed according to National Cancer Institute Common Toxicity Criteria). Ten patients developed Grade 3 leukopenia and 9 had Grade 3 neutropenia. Serious nonhematologic events were rare. There were 2 (7%) complete and 2 (7%) partial responses, for an overall response rate of 14%. Sixteen (55%) patients had stable disease and 9 (31%) experienced disease progression.

CONCLUSIONS

A 3‐day regimen of topotecan at a dose of 2.0 mg/m2 per day was generally well tolerated, although the response rate was lower than that for the standard 5‐day schedule. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11690
The development of bladder tumors and contralateral upper urinary tract tumors after primary transitional cell carcinoma of the upper urinary tract
Authors: Kang Chih‐Hsiung , Yu Tsan‐Jung , Hsieh Hwei‐Ho , Yang Joseph W. , Shu Kenneth , Huang Chao‐Cheng , Chiang Po‐Huang , Shiue Yow‐Ling
Published: October 2003

BACKGROUND

Contralateral, metachronous upper urinary tract (UUT) tumors after primary transitional cell carcinoma (TCC) of the UUT are reported rarely, and to the authors' knowledge the risk factors have not been determined to date. In addition, few reports have described the characteristics of recurrent bladder tumors and contralateral UUT tumors and any relation between theses tumor types.

METHODS

Statistical analysis of data from 223 patients with documented primary UUT‐TCC was undertaken. After excluding bilateral involvement and distant metastases, 12 variables were analyzed by multivariate analysis in 189 patients to determine the risk factors for recurrent urothelial tumors.

RESULTS

The incidence rates of recurrent bladder tumors and contralateral UUT tumors were 31.2% and 5.8%, respectively. Multiplicity was determined as a risk factor for recurrent bladder tumors. Renal insufficiency, uremia, and concurrent bladder tumors significantly predisposed patients to develop contralateral UUT tumors after primary UUT‐TCC. The time intervals and stage distributions differed significantly between recurrent bladder tumors and contralateral UTT tumors. Patients who had recurrent bladder tumors had earlier stage tumors and had a shorter time to recur compared with patients who had contralateral, metachronous UUT tumors.

CONCLUSIONS

For patients with primary UUT‐TCC, regular follow‐up by cystoscopy is necessary to detect recurrent bladder tumors. Intravenous urography or retrograde pyelography should be performed for patients who have a high risk of developing contralateral UUT tumors. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11691
XRCC3 genetic polymorphism, smoking, and lung carcinoma risk in minority populations
Authors: Wang Yunfei , Liang Dong , Spitz Margaret R. , Zhang Kerang , Dong Qiong , Amos Christopher I. , Wu Xifeng
Published: October 2003

BACKGROUND

The XRCC3 protein participates in DNA double‐strand breaks and recombinational repair. A single C‐to‐T nucleotide change at codon 241 (Thr241Met) has been identified in the XRCC3 gene. Using a hospital‐based case–control approach, the authors studied the XRCC3 polymorphism as a possible genetic risk factor for lung carcinoma in African Americans and Mexican Americans.

METHODS

A total of 112 patients with lung carcinoma were frequency matched with 190 control participants on the basis of age, gender, and ethnicity. Polymerase chain reaction‐restriction fragment length polymorphism molecular analysis was used successfully to identify the XRCC3 polymorphism in peripheral blood lymphocytes.

RESULTS

No significant association between the XRCC3 variant allele polymorphism (odds ratio [OR], 1.25; 95% confidence interval [95% CI], 0.72–2.15) and lung carcinoma risk was noted. However, a significantly increased risk for lung carcinoma (OR, 5.20; 95% CI, 1.59–17.03) was evident in heavy smokers with the variant T‐allele genotypes. Furthermore, a joint effect of the T‐allele and heavy smoking was observed (OR, 37.31; 95% CI, 11.43–121.72).

CONCLUSIONS

The XRCC3 polymorphism appeared to be associated with increased risk of lung carcinoma in certain subgroups. It is plausible that the association is very heavily dependent on the degree of smoking. Further studies with larger sample sizes will be necessary to confirm these findings. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11692
The clinical significance of soluble CD86 levels in patients with acute myeloid leukemia and myelodysplastic syndrome
Authors: Hock Barry D. , McKenzie Judith L. , Patton William Nigel , Haring Lisa F. , Yang Ying , Shen Yu , Estey Elihu H. , Albitar Maher
Published: October 2003

BACKGROUND

Levels of the soluble form of CD86 (sCD86) are elevated in a proportion of patients with leukemia. Although it is a potential modulator of antitumor responses, the significance of sCD86 in patients with hematologic malignancies is unknown.

METHODS

The authors evaluated sCD86 levels by enzyme‐linked immunosorbent assay in patients with acute myeloid leukemia (AML) (n = 57 patients) and patients with myelodysplastic syndrome (MDS) (n = 40 patients) and analyzed the relation between sCD86 levels and various clinical parameters.

RESULTS

Levels of sCD86 were elevated (> 2.32 ng/mL) relative to normal donors (0.22–2.32 ng/mL; n = 51 patients) in 25% of patients with AML and in 27% of patients with MDS. Patients with AML who had elevated sCD86 levels had significantly lower complete remission (CR) rates compared with patients with AML who had normal sCD86 levels. In multivariate analysis using sCD86 as a continuous variable and including the interaction of age and sCD86 as a variable, sCD86 was a significant prognostic factor (P = 0.014) independent of cytogenetics. Further analysis demonstrated that, in patients with AML age 60 years and younger, but not in patients older than 60 years, elevated sCD86 levels were associated with significantly shorter survival (P = 0.04). There was no correlation between sCD86 levels and CR rates or survival in patients with MDS.

CONCLUSIONS

The presence in patients with AML of elevated levels of circulating sCD86 were associated with lower CR rates and poor survival. The prognostic significance of sCD86 was independent of cytogenetics but was modulated by age, in that it was independently significant only in younger patients. The results suggest that sCD86 may play a role in modulating immune responses associated with the progression of AML. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11693
Motility‐related protein 1 (MRP‐1/CD9) expression in urothelial bladder carcinoma and its relation to tumor recurrence and progression
Authors: Mhawech Paulette , Herrmann Françoís , Coassin Monique , Guillou Louis , Iselin Christophe E.
Published: October 2003

BACKGROUND

CD9 has been implicated in cell adhesion, motility, and proliferation, and numerous studies have demonstrated its prognostic value in different solid tumors. The objective of this study was to determine the relation of CD9 expression to tumor grade and tumor stage of urothelial carcinoma of the bladder and to define the value of CD9 in predicting the behavior of superficial papillary tumors (SPTs) (pathologic Ta [pTa] and pT1).

METHODS

Three hundred twenty patients (118 patients with pTa tumors, 111 patients with pT1 tumors, and 91 patients with pT2 tumors) were examined for CD9 expression using immunohistochemistry applied on formalin fixed, paraffin embedded tissue. Patients were stratified into 3 categories, depending on CD9 expression: positive (> 50% positive cells), reduced (5–50% positive cells), or negative (< 5% positive cells).

RESULTS

Loss of CD9 expression was found to be associated significantly with high‐grade and high‐stage urothelial tumors (P < 0.0001). A reduced/negative (altered) CD9 expression was associated with SPT progression, but not with recurrence (P < 0.001). Patients who had pTa or pT1 tumors with altered CD9 expression had a relative risk of 5.59 (P = 0.005; 95% confidence interval [95% CI], 1.69–18.48) for progression compared with patients who had tumors with positive CD9 expression. Kaplan–Meier curves showed that a lack of CD9 expression was associated significantly with progression free survival (P < 0.001; log‐rank test), but not with recurrence. In patients with SPTs, multivariate Cox proportional hazards regression analysis revealed that negative CD9 expression was an independent prognostic marker for the prediction of tumor progression (P = 0.007; 95% CI, 0.11–0.70).

CONCLUSIONS

In patients with urothelial bladder carcinoma, CD9 expression was associated significantly with tumor stage and grade, and a loss of CD9 expression was an independent prognostic factor for predicting progression in patients with SPTs. Thus, CD9 immunoexpression is a potential new predictor of tumor behavior in patients with SPTs of the urinary bladder. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11698
Long‐term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma
Authors: Rosen Lee S. , Gordon David , Kaminski Mary , Howell Anthony , Belch Andrew , Mackey John , Apffelstaedt Justus , Hussein Mohamad A. , Coleman Robert E. , Reitsma Dirk J. , Chen Bee‐Lian , Seaman John J.
Published: October 2003

BACKGROUND

The goal of the current study was to compare the long‐term (25‐month) safety and efficacy of zoledronic acid with pamidronate in patients with bone lesions secondary to advanced breast carcinoma or multiple myeloma.

METHODS

Patients (n = 1648) were randomized to receive 4 mg or 8 mg (reduced to 4 mg) zoledronic acid as a 15‐minute infusion or to receive 90 mg pamidronate as a 2‐hour infusion every 3–4 weeks for 24 months. The primary endpoint was the proportion of patients with at least 1 skeletal‐related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate, and multiple‐event analysis. Hypercalcemia of malignancy (HCM) was included as an SRE in some secondary analyses.

RESULTS

After 25 months of follow‐up, zoledronic acid reduced the overall proportion of patients with an SRE and reduced the skeletal morbidity rate similar to pamidronate. Compared with pamidronate, zoledronic acid (4 mg) reduced the overall risk of developing skeletal complications (including HCM) by an additional 16% (P = 0.030). In patients with breast carcinoma, zoledronic acid (4 mg) was significantly more effective than pamidronate, reducing the risk of SREs by an additional 20% (P = 0.025) compared with pamidronate and by an additional 30% in patients receiving hormonal therapy (P = 0.009). Zoledronic acid (4 mg) and pamidronate were tolerated equally well. The most common adverse events included bone pain, nausea, and fatigue.

CONCLUSIONS

Long‐term follow‐up data confirm that zoledronic acid was more effective than pamidronate in reducing the risk of skeletal complications in patients with bone metastases from breast carcinoma and was of similar efficacy in patients with multiple myeloma. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11701
Coagulopathic complications in breast cancer
Authors: Caine Graham J. , Stonelake Paul S. , Rea Daniel , Lip Gregory Y. H.
Published: October 2003

Patients with cancer are highly susceptible to thromboembolic complications, which account for a significant percentage of the morbidity and mortality of the disease. Up to 15% of patients with clinically overt cancer present with venous thromboembolism during the course of their disease. Moreover, patients with cancer represent 20% of all patients in whom deep venous thrombosis and pulmonary embolism are diagnosed. This prothrombotic state in cancer can occur due to the ability of tumor cells to directly activate the blood‐clotting cascade and cause thrombosis or induce procoagulant properties and inhibit anticoagulant properties of vascular endothelial cells, platelets, monocytes, and macrophages. It also is well established that this prothrombotic tendency in patients with cancer can be enhanced greatly by anticancer treatments, such as surgery and chemotherapy. This phenomenon can be seen in patients with breast cancer, particularly after surgery and chemotherapy. Increased clotting risk also is associated with the use of central venous access devices, commonly used to administer chemotherapeutic agents in patients with cancer. Thrombosis prophylaxis, therefore, should be considered for patients with breast cancer who are at risk before and during intervention. In the current review, the authors discuss the problem of thromboembolism in patients with breast cancer who are undergoing therapy, the mechanisms by which thromboembolisms occur, and the potential strategies by which these events may be prevented. Better understanding of these pathogenetic pathways may lead to the development of more targeted strategies to prevent thromboembolism in patients with cancer. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11702
A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma
Authors: Choi Doo Ho , Shin Dong Bok , Lee Min Hyuk , Lee Dong Wha , Dhandapani Devika , Carter Darryl , King Bonnie L. , Haffty Bruce G.
Published: October 2003

BACKGROUND

The objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early‐onset breast carcinoma.

METHODS

Sixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER‐2/neu.

RESULTS

The proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER‐2/neu. Specifically, positive HER‐2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER‐2/neu gene amplification on all HER‐2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER‐2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis.

CONCLUSIONS

The findings of high positivity of HER‐2/neu expression and gene amplification in Korean women with early‐onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti‐HER‐2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11703
A multicenter Phase I safety study of intratumoral photoactivation of talaporfin sodium in patients with refractory solid tumors
Authors: Lustig Robert A. , Vogl Thomas J. , Fromm David , Cuenca Rosa , Alex Hsi R. , D'Cruz Anil K. , Krajina Zdenko , Turić Marko , Singhal Anil , Chen James C.
Published: October 2003

BACKGROUND

Photodynamic therapy (PDT) currently is approved for the palliative treatment of malignancies of the aerodigestive tract using laser‐activated porfimer sodium. A new approach has been developed, based on intratumoral placement of a nonlaser light device that activates talaporfin sodium, that may expand the use of PDT to include a broader range of treatment‐resistant malignancies. The safety of this approach was assessed in a Phase I study in patients with locally advanced, refractory tumors.

METHODS

Twenty‐one patients with radiation‐resistant or chemotherapy‐resistant or inoperable malignancies were enrolled in four cohorts representing four light doses. Patients were treated with a single intratumoral light device and a fixed photosensitizer dose. Safety assessments were based on review of adverse events (AEs) and serious adverse events (SAEs), and independent evaluation of computed tomography (CT) images.

RESULTS

The observed occurrence of treatment‐related AEs and SAEs was minimal. No cutaneous phototoxicity was observed in any patient. The overall observed tumor response rate was 33%.

CONCLUSIONS

Photoactivation of talaporfin sodium using intratumoral nonlaser light was found to be safe in the patient population of the current study at all light dose levels tested. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11708
High time for low‐dose prospective clinical trials
Authors: DiPaola Robert S. , Durivage Henry J. , Kamen Barton A.
Published: October 2003

The article by Glode et al. in this issue reports on the empiric success, as defined by a decreased prostate specific antigen level and lack of toxicity, of metronomically delivered low‐dose chemotherapy for patients with hormone‐refractory prostate carcinoma. The data presented were collected as a retrospective evaluation of the medical records of patients treated with cyclophosphamide and dexamethasone who were unable to participate in Phase II drug trials or had failed previous chemotherapy regimens.
Prostate carcinoma risk subsequent to diagnosis of benign prostatic hyperplasia
Authors: Chokkalingam Anand P. , Nyrén Olof , Johansson Jan‐Erik , Gridley Gloria , McLaughlin Joseph K. , Adami Hans‐Olov , Hsing Ann W.
Published: October 2003

BACKGROUND

Pathologically, benign prostatic hyperplasia (BPH) is not considered a precursor for prostate carcinoma. However, because the two conditions share not only a similar hormonal environment within the prostate but also several common risk factors, it is possible that men with BPH may be at increased risk of prostate carcinoma due to these shared factors.

METHODS

To elucidate this further, the authors used Swedish nationwide population‐based record‐linkage data to assess prostate carcinoma risk up to 26 years after the diagnosis of BPH among 86,626 men.

RESULTS

Overall, relative to the general population, patients with BPH experienced little, if any, excess risk of prostate carcinoma (2% excess incidence after 10 years of follow‐up). However, patients with BPH with and without surgical intervention experienced different prostate carcinoma risk patterns. Those undergoing transvesicular adenomectomy had a significant 22% lower incidence and a 23% lower mortality after the first 5 years of follow‐up and those undergoing transurethral resection had a significant 10% higher incidence but a 17% lower mortality. In contrast, after the first 5 years, patients with BPH who did not receive surgical intervention experienced significant excesses of both prostate carcinoma incidence (18%) and mortality (77%).

CONCLUSIONS

The differences in prostate carcinoma incidence and mortality by BPH treatment type suggest that factors related to treatment or health reasons underlying the selection of treatment influence subsequent prostate carcinoma risk. Further studies are needed to confirm the minimal excess risk of prostate carcinoma among BPH patients overall and the possible impact of BPH treatment methods on subsequent prostate carcinoma risk. Cancer 2003. Published 2003 by the American Cancer Society.

DOI 10.1002/cncr.11710
Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers
Authors: Habuchi Tomonori , Kamoto Toshiyuki , Hara Isao , Kawai Koji , Nakao Masahiro , Nonomura Norio , Kobayashi Takashi , Ogawa Osamu , Kamidono Sadao , Akaza Hideyuki , Okuyama Akihiko , Kato Tetsuro , Miki Tsuneharu
Published: October 2003

BACKGROUND

A standard concept for the integration of surgery into the chemotherapy‐based treatment of patients with advanced germ cell carcinoma has been that surgery should be avoided in patients with serum tumor markers (α‐fetoprotein [AFP] and human chorionic gonadotropin [HCG]) that remain elevated. However, some patients may benefit from resection under such chemorefractory conditions. The objective of this retrospective study was to clarify the outcome and clinical prognostic variables of salvage surgery in patients with disseminated (AJCC Stage II or III) testicular germ cell carcinoma or extragonadal germ cell carcinoma who had elevated serum markers.

METHODS

The authors reviewed the clinical records of 24 patients who underwent salvage surgery with elevated serum AFP and/or HCG levels after at least 3 courses of cisplatin‐based, systemic chemotherapy between January, 1985 and December, 2000. The survival rates were compared between the subgroups with regard to preoperative and postoperative clinical parameters using the Kaplan–Meier method and a Cox proportional hazards model.

RESULTS

Ten of 24 patients (41.7%) were rendered free of disease and alive without disease after the surgery with or without adjuvant therapy at a median follow‐up of 74 months (range, 24–207 months). Among the preoperative parameters, high HCG levels were associated with significantly poorer survival (hazard ratio [HR], 8.321; 95% confidence interval [95% CI], 1.0753–64.553; P = 0.043 and P = 0.016, respectively; log‐rank test). In addition, patients who had visceral lesions at resection had a significantly poorer prognosis compared with patients who had retroperitoneal and/or mediastinal lymph node lesions (P = 0.038; log‐rank test). Among postoperative parameters, incomplete resection and persistently high HCG levels were associated significantly with poor survival, with a risk of death from disease of 12.516‐fold (95% CI, 1.786–87.781) and 9.311‐fold (95% CI, 1.796–48.256), respectively.

CONCLUSIONS

Salvage surgery in patients with high serum tumors markers resulted in long‐term disease free status in approximately 40% of patients in a small subset with advanced germ cell carcinoma. Patients with elevated AFP levels alone (i.e., normal HCG levels) or with lymph node lesions alone seem to be good candidates for such surgery. Complete resection of target lesions and normalization of HCG levels after surgery are mandatory to achieve long‐term disease free status. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11711
Response assessment classification in patients with advanced renal cell carcinoma treated on clinical trials
Authors: Schwartz Lawrence H. , Mazumdar Madhu , Wang Liang , Smith Alex , Marion Stephanie , Panicek David M. , Motzer Robert J.
Published: October 2003

BACKGROUND

The objective of the current study was to evaluate the effect on response assessment classification in patients with metastatic renal cell carcinoma (RCC) using unidimensional (Response Evaluation Criteria in Solid Tumors) and bidimensional (World Health Organization) criteria, including or excluding measurements of the primary renal tumor and using a new index to compensate for the disproportionate effect of large renal tumors relative to their metastases.

METHODS

Fifty‐three imaging studies involving a total of 44 patients with metastatic RCC who were treated on clinical trials of interferon‐α analogue and/or thalidomide were reviewed retrospectively. The best overall response assessment and progression free survival were calculated with both unidimensional and bidimensional tumor measurements. Patients were then stratified into two groups: patients with primary renal tumors in situ and patients who underwent resection of their primary renal tumors. The best overall response and the time to disease progression were calculated based on the sum of measurements (conventional methodology), both including and excluding the primary tumor. A new method of response assessment, the ‘normalized lesion index’, which equalizes the differences in tumor size for an individual patient, was evaluated and compared with the conventional response assessment.

RESULTS

There was an 11% disagreement rate in the best overall response assessment between unidimensional and bidimensional measurements. The time to progression was 9.2 months measured unidimensionally, compared with 6.4 months assessed bidimensionally. In the group of patients who had primary renal tumors in situ, using the conventional sum of measurements method, the apparent time to progression was an average of 4.2 months longer compared with measurements that did not include the primary renal tumor. The use of the normalized lesion index method resulted in an improved concordance in best overall response assessments and similar time to progression assessments when the primary renal tumor was included compared with patients who did not have primary renal tumors in situ.

CONCLUSIONS

The use of unidimensional measurements in RCC therapy assessment results in significantly different time to progression classification compared with the use of bidimensional measurements. Response assessment classification in patients with RCC is affected by the exclusion or inclusion of measurements of the primary renal tumor. The normalized lesion index warrants further study in assessing response in patients with metastatic RCC and other solid tumor malignancies that often show substantial differences in sizes of measurable lesions. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11712
Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma
Authors: Glode L. Michael , Barqawi Albaha , Crighton Frances , Crawford E. David , Kerbel Robert
Published: October 2003

BACKGROUND

The current study was designed to evaluate the efficacy and toxicity of the continuous oral administration of a combination of cyclophosphamide (50 mg/day given in the morning) and dexamethasone (1 mg/day given in the evening) in patients with prostate specific antigen (PSA) progression despite single or multiagent hormone therapy and antiandrogen withdrawal.

METHODS

The authors retrospectively evaluated the medical records of all patients with prostate carcinoma who were treated with dexamethasone and cyclophosphamide and who were unable to participate in Phase II drug trials or had failed previous chemotherapy regimens.

RESULTS

Using clinical response guidelines set forth by the Prostate Specific Antigen Working Group, 29% of patients were found to have a ≥ 80% reduction in PSA, 39% were found to have a 50–79% reduction in PSA, 6% were found to have a < 50% decrease in PSA, and 26% experienced disease progression while receiving treatment. The duration of response was 8 months (95% confidence interval [95% CI], 4–10 months). The duration of treatment was 9 months (95% CI, 6–14 months). The treatment was reported to be well tolerated with side effects being primarily bruising, Cushingoid facies, and gastrointestinal distress.

CONCLUSIONS

In the current study, low‐dose dexamethasone and cyclophosphamide demonstrated efficacy as salvage therapy in the treatment of patients with hormone‐refractory prostate carcinoma. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11713
Endometriosis‐associated ovarian carcinoma
Authors: del Carmen Marcela G. , Smith Sehdev Anne E. , Fader Amanda Nickles , Zahurak Marianna L. , Richardson Michael , Fruehauf John P. , Montz F. J. , Bristow Robert E.
Published: October 2003

BACKGROUND

Multiple epidemiologic and histologic studies have suggested that ovarian endometriosis can give rise to malignant ovarian tumors, primarily those of epithelial origin. The progression of endometriosis to endometriosis‐associated ovarian carcinoma (EAOC) has not been investigated thoroughly and is poorly understood at best. Using immunohistochemical methods, we compared the differential expression patterns of various cytokines and growth factors in atypical endometriosis (AE) and EAOC.

METHODS

Using the Johns Hopkins Pathology Data Bank, tissue blocks from patients diagnosed with EAOC or AE were identified. Tissue blocks were stained for 4 markers: vascular endothelial growth factor (VEGF), Ki‐67, estrogen receptor (ER), and progesterone receptor (PR).

RESULTS

Seventeen cases of EAOC and 8 cases of AE were identified. Staining for VEGF was documented in 16 of 17 (94%) EAOC tissue blocks and in only 1 of 8 (12.5%) AE tissue blocks (P < 0.0001). Only 4 of the 17 (23%) EAOC tissue blocks exhibited positive staining for ER, compared with 8 of 8 (100%) AE tissue blocks (P = 0.0005). Positive staining for PR was noted in only 6 of 17 (35%) EAOC samples but was present in 8 of 8 (100%) AE samples (P = 0.003). Seventy percent of EAOC samples exhibited positive staining for Ki‐67, compared with 37.5% of AE samples (P = 0.19).

CONCLUSIONS

EAOC appears to be associated with overexpression of VEGF and reduced expression of both ER and PR. Variations in VEGF expression may be associated with the malignant transformation of endometriosis and may present both diagnostic and therapeutic options for the treatment of ovarian malignancies. Cancer 2003. © 2003 American Cancer Society.

DOI 10.1002/cncr.11714