bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of esorubicin in recurrent malignant lymphoma: a Southwest Oncology Group study.
Authors: Miller T P , Dahlberg S , Salmon S E , Williamson S K , Belt R J , Dana B W , Fisher R I
Published: February 2017

A phase II trial of esorubicin (4' deoxydoxorubicin) was conducted by the Southwest Oncology Group in 88 assessable patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) at the time of first relapse. Esorubicin was administered at two dose levels: 25 mg/m2 for patients at risk for excessive myelosuppression, and at 30 mg/m2 for all others at 21-day intervals. Overall, 33 of 88 patients (38%) responded to treatment including three complete remissions (CRs; 3%) and 30 partial remissions (PRs; 34%), with the median duration of response lasting 6.2 months. Response rates did not differ significantly by histologic subtype: 31% of 26 patients with favorable NHL, 33% of 43 patients with unfavorable NHL, and 58% of 19 patients with HD. Twelve of 33 responding patients (36%) had relatively durable remissions lasting from 1 to more than 4 years. Leukopenia (less than 3,000 cells per microliter) was seen in 65 of 88 patients (74%) and was severe (less than 1,000 cells per microliter) in 20 of 88 patients (23%). Clinical signs or symptoms of congestive heart failure were not seen and the ejection fraction (EF) fell 10% to 20% in three patients. Esorubicin is an active agent in patients with NHL or HD at the time of first relapse.
Regimen-related toxicity of a busulfan-cyclophosphamide conditioning regimen in 70 patients undergoing allogeneic bone marrow transplantation.
Authors: Nevill T J , Barnett M J , Klingemann H G , Reece D E , Shepherd J D , Phillips G L
Published: February 2017

The regimen-related toxicity (RRT) of a busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) conditioning regimen (BuCy) was evaluated in 70 consecutive patients undergoing allogeneic bone marrow transplantation for hematologic malignancies. Patients were given toxicity gradings retrospectively in each of eight organ systems (cardiac, bladder, renal, pulmonary, hepatic, CNS, stomatic, and gastrointestinal) according to a recently developed RRT scale. A set of patient, disease, and treatment parameters (age, sex, diagnosis, Eastern Cooperative Oncology Group [ECOG] score, preconditioning liver function tests [LFT], prior chemotherapy exposure, disease status, graft-versus-host disease [GVHD] prophylaxis, antimicrobial agent use, hematologic recovery, and severity of acute GVHD) was statistically analyzed to determine significant predictors of RRT. The most common significant organ toxicities were stomatic (87% of patients; 63% grades II to IV) and hepatic (83% of patients; 44% grades II to IV). Renal and gastrointestinal toxicities were not uncommon (35% and 27%, respectively) but were rarely serious (9% and 1% grades II to IV, respectively). Twelve patients developed grade III toxicities of the following systems: hepatic (seven), pulmonary (two), bladder (two), and CNS (one). Females had more frequent stomatitis (P = .04) and hepatic RRT (P = .004). Patients receiving methotrexate in their GVHD prophylactic regimen experienced more grade II to IV stomatitis (P = .04) and hepatic RRT (P = .04). The use of amphotericin B (P = .01) or prolonged antibiotic courses (P = .04) was associated with more grades II to IV hepatic RRT. In a multivariate analysis, only amphotericin B administration predicted grades II to IV hepatic RRT (P = .01). The incidence of acute GVHD was 49%, with 31% having grades II to IV GVHD. The estimated 2-year event-free survival (EFS) for the entire study group was 44%. The estimated 2-year EFS was 63% for standard-risk patients (acute leukemia in first remission and chronic myelogenous leukemia [CML] in first stable phase) and 24% for all others (high-risk patients). High-risk patients were at increased risk of disease recurrence and RRT. BuCy is an efficacious bone marrow transplant conditioning regimen for standard-risk patients with leukemia but has significant associated hepatic RRT.
Phase I–II Studies of Yttrium-Labeled Antiferritin Treatment for End-Stage Hodgkin's Disease, Including Radiation Therapy Oncology Group 87-01
Authors: Vriesendorp H.M. , Herpst J.M. , Germack M.A. , Klein J.L. , Leichner P.K. , Loudenslager D.M. , Order S.E.
Published: February 2017

Figure 2 of the report "Phase I–II Studies of Yttrium-Labeled Antiferritin Treatment for End-Stage Hodgkin's Disease, Including Radiation Therapy Oncology Group 87-01" by Vriesendorp et al (J Clin Oncol 9:918–928) was presented incorrectly. It is shown here without error:

Please see the PDF for Figure.
The significance of circulating cells carrying t(14;18) in long remission from follicular lymphoma.
Authors: Price C G , Meerabux J , Murtagh S , Cotter F E , Rohatiner A Z , Young B D , Lister T A
Published: February 2017

Peripheral blood mononuclear cell fractions from 15 patients in continuous clinical remission from follicular lymphoma for longer than 10 years were examined for cells carrying the t(14;18) translocation using the polymerase chain reaction (PCR). The assay used was able to detect one positive cell in approximately 5 x 10(5) cells (a single 14q+ molecule in 2.5 micrograms DNA). Cells positive for t(14;18) were found in six of eight patients initially presenting with stage III or IV disease, compared with zero of seven of those with stage I or II disease (P less than .05). In two cases 14q+ junction regions were also successfully amplified from formalin-fixed biopsy material obtained at presentation 12 and 17 years previously. In both, sequence analysis demonstrated that the cells circulating in remission belonged to the original clone. These results indicate that cells bearing t(14;18) frequently persist in the peripheral blood in long remission of advanced follicular lymphoma and question the value of their presence as a predictor of relapse.
Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia.
Authors: Forman S J , Schmidt G M , Nademanee A P , Amylon M D , Chao N J , Fahey J L , Konrad P N , Margolin K A , Niland J C , O'Donnell M R
Published: February 2017

The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long-term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy.
Importance of bone marrow cytogenetic evaluation before autologous bone marrow transplantation for Hodgkin's disease.
Authors: Chao N J , Nademanee A P , Long G D , Schmidt G M , Donlon T A , Parker P , Slovak M L , Nagasawa L S , Blume K G , Forman S J
Published: February 2017

Alkylating agents used either with or without radiation therapy have been associated with the development of myelodysplastic syndrome (MDS) and acute nonlymphoblastic leukemia (ANLL) after treatment of both malignant and nonmalignant disorders. This report describes seven patients with recurrent Hodgkin's disease (HD) evaluated for bone marrow transplantation (BMT) who developed chromosomal abnormalities, and emphasizes the importance of bone marrow cytogenetic studies before bone marrow harvest. Three patients with histologically normal bone marrow underwent autologous BMT and subsequently developed an MDS or ANLL. Four patients had the clonal abnormality detected before bone marrow harvest and did not proceed to BMT.
Sequences of taxol and cisplatin: a phase I and pharmacologic study.
Authors: Rowinsky E K , Gilbert M R , McGuire W P , Noe D A , Grochow L B , Forastiere A A , Ettinger D S , Lubejko B G , Clark B , Sartorius S E
Published: February 2017

Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated.
A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.
Authors: Raats J I , Falkson G , Falkson H C
Published: February 2017

PURPOSE

The study investigated the therapeutic effects of fadrozole (CGS 16949A), a new aromatase inhibitor, in women who had received prior treatment for metastatic breast cancer.

MATERIALS AND METHODS

Eighty postmenopausal women who had received prior treatment for metastatic breast cancer were randomized to receive fadrozole 1 mg/d or 4 mg/d per day orally. Seventy-eight patients were assessable for toxicity and response.

RESULTS

Toxicity was limited to mild (grade 1) to moderate (grade 2) hot flashes in 28%, nausea and vomiting in 13%, fatigue in 8%, and mild loss of appetite in 5% of patients. No electrolyte or unanticipated hormonal changes occurred. The overall response was 23% (complete response, 10%; partial response, 13%). In addition, 45% of the patients had a no change status. There was no difference in response rate between the patients randomized to the two different doses of fadrozole. Only dominant site of metastases significantly affected response. The median time to treatment failure (TTF) was 4.4 months (4.7 months on 1 mg/d and 3.7 months on 4 mg/d). The median survival was 22.6 months (17.5 months on 1 mg/d; median survival has not been reached in patients on 4 mg/d). The response and survival in patients with estrogen receptor (ER)-positive and ER-unknown disease were not significantly different.

CONCLUSIONS

Fadrozole has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer. In this study there was no significant difference in toxicity or response between 1 mg/d and 4 mg/d. Further trials comparing fadrozole to other hormone treatment are indicated.
Pain, opioid use, and survival in hospitalized patients with advanced cancer.
Authors: Brescia F J , Portenoy R K , Ryan M , Krasnoff L , Gray G
Published: February 2017

PURPOSE

Pain is a common and feared symptom for patients with incurable cancer. Comprehensive assessment provides the foundation for effective pain management, and data that clarify the relationship between pain and other relevant factors also facilitate this process. The main objective of the study was to develop a clinical data base for advanced cancer patients and to survey data to determine (1) pain severity at admission, (2) opioid use at admission, (3) change in opioid use during the hospital stay, and (4) survival in the hospital.

PATIENTS AND METHODS

Information was collected prospectively on 1,103 patients admitted and on 1,017 patients who died within 6 months of the study's end. Demographic and clinical data were recorded 72 hours after admission and soon after death or discharge.

RESULTS

Seventy-three percent of patients had pain at admission. Cancer of the cervix was frequently (68%) associated with severe pain, as were prostate (52%) and rectal/sigmoid tumors (49%). Severe pain was more probable in those with bone metastasis, those admitted from home, and in those younger than 55 years of age. The majority (71.7%) of patients had a stable dosing pattern, and only 4.2% of the patients required dose increases of at least 10% per day.

CONCLUSION

This study demonstrated the wide variability in opioid doses required. No reliable predictor of opioid requirement was identified, and this lack of predictability of cancer pain severity underscores the need for ongoing assessment.
Acute lymphoblastic leukemia occurring as a second malignant neoplasm in childhood: report of three cases and review of the literature.
Authors: Hunger S P , Sklar J , Link M P
Published: February 2017

PURPOSE

The long-term effects of childhood cancer and its therapy are a problem of increasing concern. One of the most important of these late effects is the development of second malignant neoplasms (SMNs), which occur in approximately 8% of children within 20 years of diagnosis of a malignancy. These secondary cancers may result (individually or in combination) from increased genetic susceptibility, the mutagenic effects of chemotherapy and/or radiation therapy, or chance. Whereas the development of acute nonlymphocytic leukemia (ANLL) as an SMN is a well-recognized phenomenon, acute lymphoblastic leukemia (ALL) has been infrequently described as an SMN in either adults or children.

PATIENTS AND METHODS

We report three patients treated at our institution in whom ALL developed as an SMN after treatment for neuroblastoma, Wilms' tumor, and Hodgkin's disease. These cases prompted us to review the published literature for cases of secondary ALL in childhood. Patients whose initial malignancy was diagnosed at age less than 16 years were classified as pediatric patients. SMNs were defined as cancers of clearly distinct histologic type occurring 6 or more months after diagnosis of the first malignant neoplasm.

RESULTS

Including the three index cases, a total of 18 children with secondary ALL are reviewed, and the clinical features are discussed and compared with those of secondary ANLL.

CONCLUSIONS

This review summarizes the published case histories of secondary ALL. The data suggest that ALL represents approximately 5% to 10% of the cases of acute leukemia that arise as SMNs in both adults and children.
On the bioavailability of oral and subcutaneous 2-chloro-2'-deoxyadenosine in humans: alternative routes of administration.
Authors: Liliemark J , Albertioni F , Hassan M , Juliusson G
Published: February 2017

PURPOSE

The antimetabolite 2-chloro-2'-deoxyadenosine (CdA) is a promising alternative to alkylating agents for the treatment of lymphoproliferative disorders. Its use, however, is hampered by the need for intravenous (IV) administration. The aim of the present study was to determine the bioavailability of subcutaneously (SC) and orally administered CdA, and to establish an oral dose of CdA that could supersede IV administration.

PATIENTS AND METHODS

A previously developed high-performance liquid chromatography method was used for the determination of plasma CdA concentrations in 13 patients. Ten patients were treated on alternate days with 0.14 mg/kg/d CdA as a 2-hour IV infusion or by a SC injection. Three of these patients were also given 0.14 mg/kg CdA orally in enteric-coated capsules. Ten patients were administered CdA orally that was dissolved in phosphate-buffered saline (PBS) after treatment with 20 mg omeprazole 1 and 6 hours before the administration of CdA.

RESULTS

The bioavailability of SC CdA was 102% +/- 28% (mean +/- SD), and the bioavailability of CdA administered in enteric-coated capsules was 19%, 24%, and 60%. In the three patients who were given 0.14 mg/kg orally dissolved in PBS, the bioavailability was 48% +/- 8%, whereas in the seven patients who received 0.28 mg/kg, the bioavailability was 55% +/- 17%. In the 10 patients who were treated with the CdA solution orally, the coefficients of variation of the areas under the curve (AUCs) after oral and IV administration were similar. Thus, oral administration did not add to the interindividual variability.

CONCLUSIONS

We conclude that orally administered CdA can supersede IV infusion if the dose is doubled. SC administration gives a high peak concentration of short duration with an AUC identical to that of IV infusion. Thus, SC injection can also be used as an alternative to IV infusion.
Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.
Authors: Diel I J , Kaufmann M , Goerner R , Costa S D , Kaul S , Bastert G
Published: February 2017

PURPOSE

At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse.

PATIENTS AND METHODS

Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas.

RESULTS

A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection.

CONCLUSIONS

This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.
Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.
Authors: Hoskins P J , O'Reilly S E , Swenerton K D , Spinelli J J , Fairey R N , Benedet J L
Published: February 2017

PURPOSE

At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed.

PATIENTS AND METHODS

One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission.

RESULTS

The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor.

CONCLUSIONS

Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.
Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer.
Authors: Hudes G R , Greenberg R , Krigel R L , Fox S , Scher R , Litwin S , Watts P , Speicher L , Tew K , Comis R
Published: February 2017

PURPOSE

Estramustine phosphate (EMP) and vinblastine are two microtubule inhibitors with distinct molecular targets and at least additive antimicrotubule effects in vitro. Their modest single-agent activities in hormone-refractory prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted a phase II trial in hormone-refractory prostate cancer.

PATIENTS AND METHODS

Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1 to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses were repeated every 8 weeks. Response assessment was based on a change in serum prostate-specific antigen (PSA) levels and was correlated with change in pain scores.

RESULTS

PSA decreased from baseline by at least 50% in 22 patients (61.1%) and by > or = 75% in eight patients (22.2%). A 50% or more decrease in PSA on three successive 2-week measurements together with an improved or stable pain score, performance status, and measurable soft tissue disease (if present) was required for a partial response (PR), which occurred in 11 patients for an overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In seven patients with measurable nonosseous disease, there was one PR (14%) and one minor response (MR). In 28 patients with assessable pain, major pain responses occurred in 12 (42.9%). PSA response (> or = 50% decrease times three measurements) was predictive of major pain response with a 93.7% specificity, a 50% sensitivity, and a positive predictive value of 85.7%.

CONCLUSION

We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.
Consolidation hemibody radiotherapy following induction combination chemotherapy in high-tumor-burden multiple myeloma.
Authors: MacKenzie M R , Wold H , George C , Gandara D , Ray G , Schiff S , Shields J , Artim R , Davidson H , Meyers F
Published: February 2017

PURPOSE

Curative therapy for multiple myeloma continues to be an elusive goal. This report discusses the Northern California Oncology Group (NCOG) phase I and II trial in high-tumor-burden disease that used a strategy that consisted of induction chemotherapy (vincristine, melphalan, cyclophosphamide, and prednisone [VMCP]) for eight cycles followed by sequential hemibody radiation therapy (RT) and subsequent chemotherapy for an additional eight cycles.

PATIENTS AND METHODS

Seventy-two previously untreated stage III myeloma patients were entered onto the study. Sixty-nine received induction chemotherapy, 40 received induction chemotherapy and hemibody RT, and 23 received induction chemotherapy, hemibody RT, and consolidative chemotherapy.

RESULTS

Twenty-two complete responses (CRs) were obtained by induction chemotherapy, with four additional CRs after RT and consolidative chemotherapy. Nineteen patients developed grade 4 hematologic toxicity primarily after upper hemibody RT. Eight of these developed long-standing neutropenia or thrombocytopenia. Median survival of the group was 134 weeks, which was not significantly different from other approaches.

CONCLUSIONS

Hemibody RT can be combined with chemotherapy as induction therapy and can be safely administered in a community setting. However, as administered here no survival advantage was demonstrated.
Ethical issues in phase I oncology research: a comparison of investigators and institutional review board chairpersons.
Authors: Kodish E , Stocking C , Ratain M J , Kohrman A , Siegler M
Published: February 2017

PURPOSE

Phase I research trials assess the safety of agents never before administered to humans. In the field of oncology, this practice raises several important ethical questions. We examined the ethics of these trials by surveying phase I oncology investigators and institutional review board (IRB) chairpersons at major cancer research centers around the country.

METHODS

Questionnaires were mailed to 78 investigators and 47 chairpersons to obtain their views on the ethical propriety of conducting phase I oncology research, and on institutional practice regarding these trials. The response rate was 68% in each group.

RESULTS

The majority of each group reported that phase I oncology trials face no more scrutiny or resistance in their institution's IRB process than other research protocols. Nevertheless, IRB chairpersons were more likely than investigators to favor special procedural safeguards to protect subjects in phase I oncology trials. Nearly all respondents agreed that although actual medical benefit was very uncommon, most patients entered for a chance at a therapeutic effect. Investigators were more likely than chairpersons to report that patients obtained psychologic benefit from participation in phase I trials.

CONCLUSION

Although individual IRB chairpersons and oncology investigators may have important differences of opinion concerning the ethics of phase I trials, these disagreements do not represent a widespread area of ethical conflict in clinical research.
Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. Australian New Zealand Breast Cancer Trials Group.
Authors: Coates A , Gebski V , Signorini D , Murray P , McNeil D , Byrne M , Forbes J F
Published: February 2017

PURPOSE

We observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail.

PATIENTS AND METHODS

In a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self-assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors.

RESULTS

Physician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change in scores for PWB, mood, pain, and QLI after the first three treatment cycles, but before an arbitrary 180-day time point, were significantly predictive of survival beyond that time. Both QLI and PWB were prognostically independent of tumor response. Although QL improvement was correlated with tumor response, continuous therapy yielded significantly better QL scores, even in nonresponders.

CONCLUSION

These findings support the validity of the simple QL measures used in the trial. They are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration.
Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study.
Authors: Niiranen A , Niitamo-Korhonen S , Kouri M , Assendelft A , Mattson K , Pyrhönen S
Published: February 2017

PURPOSE

The aims of this study were to assess the effect of adjuvant chemotherapy on overall survival, disease-free survival, and relapse pattern, as well as its toxicity in patients who underwent radical surgery for non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

One hundred ten patients with T1-3N0 (World Health Organization [WHO] 1981) NSCLC underwent radical surgery during the period of 1982 through 1987. After surgery, the patients were randomized to receive adjuvant chemotherapy (n = 54) (cyclophosphamide 400 mg/m2, doxorubicin 40 mg/m2, and cisplatin 40 mg/m2 [CAP] for six cycles) or no active treatment (n = 56).

RESULTS

After 10 years from the start of the study, 61% of patients were alive in the chemotherapy group and 48% were alive in the control group (P = .050). Seventeen patients (31%) in the CAP group and 27 patients (48%) in the control group had a recurrence during the follow-up period (P = .01). The 5-year survival rate was 67% in the chemotherapy group and was 56% in the control group (P = .050). The patients in the chemotherapy group who completed the planned treatment had a slightly better 5-year survival than those whose chemotherapy was discontinued (72.5% v 50.3%; P = .15). Chemotherapy-related gastrointestinal toxicity grade 3 to 4 (WHO) occurred in 63% and was the main reason why patients refused further planned therapy.

CONCLUSION

Our results suggest that patients with NSCLC at pathologic stage I who have undergone radical surgery benefit from adjuvant chemotherapy.
Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.
Authors: Verdonck L F , Dekker A W , de Gast G C , van Kempen M L , Lokhorst H M , Nieuwenhuis H K
Published: February 2017

PURPOSE

We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy.

PATIENTS AND METHODS

Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT.

RESULTS

Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity.

CONCLUSION

ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.
A prospective study of a new combination chemotherapy regimen in patients older than 70 years with unfavorable non-Hodgkin's lymphoma.
Authors: Tirelli U , Zagonel V , Errante D , Serraino D , Talamini R , De Cicco M , Carbone A , Monfardini S
Published: February 2017

PURPOSE

A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma (NHL), was undertaken.

PATIENTS AND METHODS

Between January 1987 and April 1990, 52 consecutive unselected patients older than 70 years (median age, 75.6 years) with stage I to IV intermediate- and high-grade NHL, or with stage III to IV low-grade malignancy with symptomatic disease received etoposide and prednimustine 80 mg/m2 orally for 5 days and mitoxantrone 8 to 10 mg/m2 day 1 intravenously (IV), every 21 days. Fourteen patients were previously treated.

RESULTS

Among the 48 assessable patients, the objective response rate was 81%; 46% of the patients achieved a complete response (CR). The overall toxicity seemed to be acceptable, with 15 (7%) episodes of grade 4 leukopenia and 41 (18%) episodes of grade 3, over a total of 226 administered cycles. The median survival was 12 months. The patients who obtained CR have a longer survival than those who did not (34 v 8 months; P less than .001). Fifty-eight percent of patients achieving CR were free from relapse at 24 months; up to 36 months from the start of therapy, 25% were free from relapse. As far as patients affected by diffuse histiocytic lymphoma, 66% of previously untreated patients obtained a CR, and 55% of them were still disease-free at 24 months from the start of therapy.

CONCLUSION

We conclude that VMP is effective, well tolerated, and feasible on an outpatient basis in an unselected, elderly population affected by unfavorable NHL.
Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.
Authors: Markman M , Hakes T , Reichman B , Lewis J L , Rubin S , Jones W , Almadrones L , Pizzuto F , Hoskins W
Published: February 2017

PURPOSE

There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting.

PATIENTS AND METHODS

Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities.

RESULTS

Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program.

CONCLUSION

Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.
Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.
Authors: Roth B J , Johnson D H , Einhorn L H , Schacter L P , Cherng N C , Cohen H J , Crawford J , Randolph J A , Goodlow J L , Broun G O
Published: February 2017

PURPOSE

The trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone.

PATIENTS AND METHODS

In this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP).

RESULTS

There were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with alternating therapy (4.3 months, 4.0 months, 5.2 months, respectively). Crossover second-line chemotherapy given at progression produced low response rates and short survival, regardless of the regimen used. Myelosuppression was the dose-limiting toxicity for all patients, although the pattern and severity differed among the treatment arms.

CONCLUSIONS

The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant. Alternating therapy provides no therapeutic advantage compared with the use of either of these regimens alone and should not be considered as standard treatment in this clinical setting.
Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma.
Authors: Wazer D E , DiPetrillo T , Schmidt-Ullrich R , Weld L , Smith T J , Marchant D J , Robert N J
Published: February 2017

PURPOSE

The study was undertaken to assess the relationship among cosmesis and complications to factors related to disease presentation, surgical and radiotherapeutic technique, and adjuvant systemic therapy in conservative treatment for early-stage breast carcinoma.

PATIENTS AND METHODS

Between 1982 and 1988, 234 women with stage I/II breast carcinoma were treated with conservation therapy by a highly standardized protocol of limited excision and radiotherapy. Radiation boost and/or reexcision were determined by careful quantitation of the normal tissue margin around the primary tumor. Boosts to 20 Gy were preferentially performed with interstitial iridium-192 (192Ir) implants. Axillary node dissections were performed in all patients aged less than 70 years. Adjuvant therapy consisted of cyclophosphamide, methotrexate, (doxorubicin), and fluorouracil (CM[A]F) six to eight times for node-positive premenopausal women and tamoxifen for node-positive or -negative postmenopausal women. Median follow-up was 50 months (range, 20 to 80 months). Cosmesis was graded by defined criteria, and complications were individually scored.

RESULTS

Factors found to impact cosmesis adversely were palpable tumors (P = .046), volume of breast tissue resected (P = .027), reexcision of the tumor bed (P = .01), number of radiation fields (P = .03), radiation boost (P = .01), and chest wall separation (P = .01). There was a trend toward worse cosmesis (P = .062) in patients receiving tamoxifen. Cosmesis was not adversely affected by interstitial implant in spite of a higher prescribed dose. Factors influencing complication risk were axillary node dissection (P = .02), number of lymph nodes harvested (P = .05), and chemotherapy (P = .03).

CONCLUSIONS

Optimal cosmesis and minimal complication risk require careful attention to the technical details of surgery and radiotherapy. The impact of systemic therapies needs to be more thoroughly examined.
2-Chlorodeoxyadenosine treatment of low-grade lymphomas.
Authors: Kay A C , Saven A , Carrera C J , Carson D A , Thurston D , Beutler E , Piro L D
Published: February 2017

PURPOSE

Because of the need to identify effective new agents in the treatment of non-Hodgkin's lymphoma and because of the high activity of the purine analog 2-chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade lymphocytic lymphomas.

PATIENTS AND METHODS

Forty patients with low-grade lymphocytic lymphomas including diffuse small lymphocytic, follicular small-cleaved, and follicular mixed histologies were enrolled onto the study. Conventional therapies had failed in all patients, and six patients had lymph node biopsies showing evidence of histologic evolution to a higher-grade lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had received a median of three prior therapies (range, one to six therapies).

RESULTS

An overall response rate of 43% was achieved, with eight patients experiencing complete responses (CRs) and nine patients experiencing partial responses (PRs). The duration of responses ranged from 1 to greater than 33 months without maintenance therapy (median duration of response, 5 months). Histology and prior therapy history did not seem to correlate with responses. Significant toxicity was limited to bone marrow suppression; 18% of patients developed neutropenia, and 30% developed thrombocytopenia.

CONCLUSIONS

This phase II trial demonstrates that 2-CdA is an effective antilymphocyte, antineoplastic agent with significant activity as a single agent in patients with recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved with an acceptable toxicity profile. Further trials of this agent in previously untreated patients and in combination regimens are indicated and will be developed.
Preradiation intracarotid cisplatin treatment of newly diagnosed anaplastic gliomas. The CNS Cancer Consortium.
Authors: Dropcho E J , Rosenfeld S S , Morawetz R B , Vitek J , Brothers M , Gorum T , Bell S , Gillespie G Y , Glantz M , Mahaley M S
Published: February 2017

PURPOSE

This phase II study was performed to assess the response of patients with newly diagnosed, untreated malignant gliomas (anaplastic astrocytoma [AA] and glioblastoma multiforme [GBM]) to intracarotid (IC) cisplatin.

PATIENTS AND METHODS

Eligibility criteria included surgical intervention limited to biopsy only, measurable contrast-enhancing tumor, and unilateral tumor location within the vascular territory of one internal carotid artery. Patients were scheduled to receive four infusions of IC cisplatin (75 mg/m2 every 4 weeks) before beginning standard radiotherapy. Twenty-six patients were treated, and 22 were assessable for response.

RESULTS

Ten patients (45%) showed a greater than 25% decrease in the enhancing tumor area before radiotherapy with stabilization or improvement of neurologic deficits, and three patients (14%) had a greater than 70% decrease in tumor area. The likelihood of response to IC cisplatin was not clearly linked to patient age, tumor histology, or pretreatment tumor size. Myelosuppression, nephrotoxicity, and ototoxicity were mild. Optic neuropathy occurred in one patient, seizures in two, and fatal postinfusion cerebral edema in one.

CONCLUSION

This study design, which permits assessment of the drug sensitivity of the untreated glioma, has shown definite antitumor activity of IC cisplatin in newly diagnosed malignant glioma patients.
Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients.
Authors: Grant S C , Gralla R J , Kris M G , Orazem J , Kitsis E A
Published: February 2017

PURPOSE

This review was undertaken (1) to determine the antitumor activity of agents studied in phase II trials in small-cell lung cancer (SCLC) patients, (2) to evaluate the adequacy of published trials, (3) to determine if previously treated patients are suitable for phase II trials in SCLC, and (4) to develop an improved design for phase II trials.

DESIGN

English-language, single-agent efficacy trials in SCLC, published from 1970 to 1990, were reviewed. Study design and reporting of results were assessed for clinical and statistical methodology. Response rates observed in previously treated patients were compared with those observed in previously untreated patients.

RESULTS

One hundred forty-one articles evaluating 57 agents in 3,042 patients were reviewed. Eleven drugs were active (defined as a response rate greater than or equal to 20% in a trial with greater than or equal to 14 assessable patients), and 12 were inactive. Due to methodologic problems with the clinical trials, the usefulness of the remaining 34 drugs (60%) remains uncertain. Deficiencies identified in trials include inappropriate sample sizes, poorly defined response criteria, and failure to report important prognostic factors. When studied in adequate trials, all agents known to be active in SCLC had an observed response rate greater than or equal to 10% in previously treated patients.

CONCLUSIONS

Over the past 2 decades, phase II trials in SCLC have failed in their primary task of effectively identifying agents that warrant further clinical study and rejecting inactive agents. If only previously treated patients had been entered into these trials, no useful agent would have been missed provided that a lower observed response rate had been used as evidence of antitumor activity. We propose a two-stage sequential study design, entering previously treated patients, for future phase II trials in SCLC.
Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.
Authors: Smith D C , Tucker J A , Trump D L
Published: February 2017

PURPOSE

Hypercalcemia is a rare complication of prostate cancer, and no definite association with any histologic subtype of prostatic malignancy has been documented. We have recently seen three patients who developed hypercalcemia in the setting of prostate cancer. All had neuroendocrine carcinoma of the prostate (NCPs), which prompted an exploration of the potential association of hypercalcemia with NCP.

DESIGN

An extensive review of literature published in the English-language was conducted to identify cases of hypercalcemia associated with prostate cancer and well-documented cases of NCP.

RESULTS

We found 17 reported cases of hypercalcemia clearly associated with prostate cancer and a total of 61 cases of well-documented NCP. Including our cases, 11 of the 20 reported cases of hypercalcemia associated with prostate carcinoma were in patients with neuroendocrine carcinomas.

CONCLUSION

Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies.