bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors.
Authors: Green D M , Brecher M L , Grossi M , Simpson L , Fisher J E , Allen J E , Cooney D R , Jewett T C , Freeman A I
Published: February 2017

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.
Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy.
Authors: Vaughan W P , Karp J E , Burke P J
Published: February 2017

Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have "secondary" acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of "primary" acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively.
Failure of low-dose, total-body irradiation to augment combination chemotherapy in extensive-stage small cell carcinoma of the lung.
Authors: Dillman R O , Seagren S L , Taetle R
Published: February 2017

In a pilot study, 21 consecutive eligible patients with extensive-stage small cell carcinoma of the lung were scheduled for treatment with combination chemotherapy followed by total-body irradiation (TBI), prophylactic cranial irradiation, and consolidative chemotherapy. Induction chemotherapy consisted of VP16-213, vincristine, cyclophosphamide, and doxorubicin (VOCA). TBI was given as 100 rads in 10 fractions over 2 wk. Consolidation chemotherapy consisted of cyclophosphamide, methotrexate, and hexamethylmelamine (CMH). VOCA chemotherapy was well tolerated, with a 79% response rate in 19 evaluable patients. TBI was successfully given after four cycles of VOCA without excessive morbidity in 11 patients, although subsequent CMH chemotherapy in 8 patients has required dose reductions and some delays in therapy. Unfortunately, TBI did not increase the degree of response, and 2 patients relapsed during this therapy. Median survival in this study was 40-44 wk. One patient has survived 78 wk and remains in remission. TBI can be safely given following induction chemotherapy in extensive-stage small cell carcinoma of the lung, but it does not appear to add to the therapeutic benefit of combination chemotherapy alone.
Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer.
Authors: Lazarus H M , Herzig R H , Graham-Pole J , Wolff S N , Phillips G L , Strandjord S , Hurd D , Forman W , Gordon E M , Coccia P
Published: February 2017

Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.
Survival of women with metastatic breast cancer at Yale from 1920 to 1980.
Authors: Todd M , Shoag M , Cadman E
Published: February 2017

The tumor registry at Yale--New Haven Hospital, which began recording data in 1920, was utilized to examine the ultimate outcome of all breast cancer patients who were initially diagnosed at Yale with metastatic breast cancer. Of the 5,898 patients with breast cancer seen from 1920 to 1980, 574 initially had metastatic cancer. The median survival of these patients increased steadily from 21 months in 1920 to 41 months in the decade from 1970 to 1980. The percentage of women actually surviving 5 years increased from 5% in the 1920s to approximately 25% in the 1960s. Despite the use of combination drug programs in the 1970s, the percentage of these patients remaining alive at 5 years remained near 25%. Firm conclusions cannot be made from a retrospective study spanning 60 years, although the trends depicted and lack of continued improvement indicate that our current therapeutic approach to metastatic breast cancer may not result in dramatic improvement in overall survival.
Abdominal relapses in irradiated second National Wilms' Tumor Study patients.
Authors: Thomas P R , Tefft M , Farewell V T , Norkool P , Storer B , D'Angio G J
Published: February 2017

Ten of 259 (3.8%) irradiated patients with group 2 and 3 tumors in the second National Wilms' Tumor Study experienced initial clinical relapse either in the operative site or elsewhere in the abdomen, excluding the liver and opposite kidney. Analysis of factors associated with abdominal recurrences has shown the independent significance of unfavorable histology, field size of the radiotherapy portals, and a postoperative delay of ten or more days before starting irradiation.
Relation of in vitro colony survival to clinical response in a prospective trial of single-agent chemotherapy for metastatic melanoma.
Authors: Meyskens F L , Loescher L , Moon T E , Takasugi B , Salmon S E
Published: February 2017

We have used the effect of therapeutic agents on clonogenic growth in agar to discriminate between active and inactive agents for malignant melanoma. We report a prospective study of single-agent chemotherapy for metastatic melanoma. Forty-five separate in vitro/in vivo correlative trials were conducted in 34 patients. A number of agents were used in these evaluations, including actinomycin D, Amsacrine, bisantrene, mitoxantrone, BCNU, vinblastine, vindesine, 5-fluorouracil, MGBG, etoposide, interferon, tamoxifen, and 13-cis-retinoic acid. At the "cut-off" concentration, a colony survival less than 30% was designated as "sensitivity" and greater than 30% as "resistance." Clinical sensitivity was designated to include complete, partial, and mixed responses and was predicted in eight of 18 trials (44%). Clinical resistance (nonresponse) was predicted correctly in 24 of 27 cases (89%). Using Fisher's exact test the association of in vitro and in vivo results was significant (P = .05). These results offer further support for the concept that clonogenic assays may help select useful agents for clinical trials in metastatic melanoma.
Hairy-cell leukemia: induction of complete remission with pentostatin (2'-deoxycoformycin).
Authors: Spiers A S , Parekh S J , Bishop M B
Published: February 2017

Two men with advanced but previously untreated B cell hairy-cell leukemia were treated with low doses of pentostatin (2'-deoxycoformycin) in intermittent courses. There was prompt clearance of hairy cells from the blood, regression of splenomegaly and lymphadenopathy, and correction of anemia, thrombocytopenia, and granulocytopenia. Side effects were tolerable and myelosuppression was not observed. Both patients achieved complete remission documented by bone marrow aspiration and biopsy and radionuclide scans of liver and spleen. They remain in complete remission nine and six months, respectively, after their last treatment. Pentostatin (Warner-Lambert, Ann Arbor, Mich) is highly active in hairy-cell leukemia and merits more extensive evaluation in this disease. A woman with hairy-cell leukemia has begun treatment with pentostatin, and at ten weeks there is disappearance of gross splenomegaly and clearance of hairy cells from the blood. Bone marrow studies have not yet been repeated.
Comparison of 5-fluorouracil with ftorafur in adjuvant chemotherapies with combined inductive and maintenance therapies for gastric cancer.
Authors: Nakajima T , Takahashi T , Takagi K , Kuno K , Kajitani T
Published: February 2017

A group of 243 patients with gastric cancer was subjected to a prospective randomized trial of adjuvant chemotherapy after curative gastrectomy. One of the three arms (regimen A) is induction therapy with a three-drug combination of mitomycin C (MMC), 5-fluorouracil (5-FU), and cytosine arabinoside (ara-C) followed by intermittent oral administration of 5-FU for two years (MFC + F). In regimen B, 5-FU in regimen A is replaced by ftorafur, administered on the same schedule as regimen A (MF'C + F'). Regimen C is the control, in which patients are treated by surgery alone. Regimen A was proven effective for the suppression of relapse in the limited groups of moderately locally advanced cancer; five-year survival rates of the subset of stages I, II, and III were 72.1% with regimen A and 53.1% with regimen C (P less than .05). Regimen B yielded a better survival than the control, although the difference did not reach statistical significance. The results seem to favor 5-FU as adjuvant chemotherapy for gastric cancer.
Hepatic artery ligation and portal vein infusion for liver metastases from colon cancer.
Authors: Laufman L R , Nims T A , Guy J T , Guy J F , Courter S
Published: February 2017

Localized treatment of liver metastases from colon cancer has yielded better results than has systemic therapy. We report 19 patients with metastatic colon cancer whose bulk disease was limited to the liver, but was not amenable to surgical resection. Many of these patients had poor prognostic features: 14 had greater than 30% replacement of the liver, five had poorly differentiated tumor, and five had previously failed to respond to systemic chemotherapy. All were treated with hepatic artery ligation and portal vein infusion of chemotherapy (mitomycin C and 5-fluorouracil). Two patients (10%) died within one month postoperatively. The remaining 17 patients all improved clinically and demonstrated a marked decrease in carcinoembryonic antigen (CEA) levels. Based on follow-up physical exam, liver function tests, computed tomographic scan, and/or laparotomy, there were two complete responses, ten partial responses, four improved, and one indeterminate, for an objective response rate of 63%. Median survival of all patients was 13 months after hepatic artery ligation, and 14 months after diagnosis of liver metastases, with four patients still alive at 13+, 16+, 41+, and 61+ months after hepatic artery ligation. We believe that this form of therapy is an effective, well-tolerated alternative for patients with unresectable liver metastases.
High-dose VP-16-213 monotherapy for refractory germinal malignancies: a phase II study.
Authors: Wolff S N , Johnson D H , Hainsworth J D , Greco F A
Published: February 2017

VP-16-213 at standard dose is one of the more active agents for the treatment of germ cell tumors. In previous phase I studies, VP-16-213 has been investigated in suprastandard dose when hematopoietic reconstitution was assured by autologous bone marrow transplantation (ABMT). This phase II study was performed to explore the possibility that an augmented dose of VP-16-213 may be more active than standard dose against germ cell tumors. Eleven patients with progressive refractory germ cell tumors were treated with high-dose VP-16-213: 2,400 mg/m2 with ABMT every three to four weeks followed by 1,200 mg/m2 without ABMT. Seven patients had received VP-16-213 at standard dose prior to high-dose VP-16-213. Toxicity to high-dose VP-16-213 included severe myelosuppression, nausea, vomiting, alopecia, mucositis, and hepatitis. Of 10 evaluable patients, two complete responses and four partial responses, all of short duration, were obtained. However, some patients unresponsive to standard-dose VP-16-213 exhibited responses to the augmented-dose VP-16-213. Therefore, although more myelosuppressive, VP-16-213 may have increased activity against germ cell tumors when administered at augmented dose. High-dose VP-16-213 may be considered in designing new approaches for initial management of patients with germ cell tumors not expected to be cured with standard chemotherapy.
Combined modality induction therapy without maintenance chemotherapy for small cell carcinoma of the lung.
Authors: Feld R , Evans W K , DeBoer G , Quirt I C , Shepherd F A , Yeoh J L , Pringle J F , Payne D G , Herman J G , Chamberlain D
Published: February 2017

One hundred fifty-three patients with limited and 167 with extensive small cell carcinoma of the lung (SCCL) were evaluable for response to treatment with six courses of chemotherapy (cyclophosphamide, doxorubicin, and vincristine), irradiation to intrathoracic disease, and prophylactic cranial irradiation (PCI). No maintenance chemotherapy was given. Fifty-two percent of patients with limited disease (LD) and 10% of extensive disease patients (ED) achieved a complete response. The median survival times for LD and ED patients were 49 and 34 weeks, respectively. These results were compared to a previous experience with 147 patients who were treated with three courses of similar induction chemotherapy and thoracic irradiation, as well as one year of maintenance chemotherapy (CCNU, procarbazine, and methotrexate) but without PCI. Although the use of PCI was found to reduce the frequency of brain metastases as the site of first relapse, detailed comparisons of response rates and survival showed no significant differences between the two study populations. Prolonged maintenance chemotherapy of the type used in the first study does not favorably influence outcome after intensive induction therapy for SCCL.
Activity of sequential low-dose methotrexate and fluorouracil in advanced colorectal carcinoma: attempt at correlation with tissue and blood levels of phosphoribosylpyrophosphate.
Authors: Kemeny N E , Ahmed T , Michaelson R A , Harper H D , Yip L C
Published: February 2017

Forty-five patients with metastatic colorectal carcinoma were treated with low-dose methotrexate (MTX) and 5-fluorouracil (5-FU) given sequentially. The dose of MTX was 40 mg/m2 intravenously (IV) on days 1 and 8 followed 24 hours later by 5-FU at 600 mg/m2 IV on days 2 and 9; the drugs were recycled every 28 days. Fourteen (32%) of 43 adequately treated patients had a complete or partial response lasting a median of nine months (range, 6-15 + months). Four patients had a minor response and seven patients had stable disease for a median of nine and 10 months, respectively. Toxicity included mucositis in 28 (65%) patients, diarrhea in 18 (40%), nausea in 11 (24%), and vomiting in seven (16%). Hematologic toxicity was mild: six patients had nadir white blood cell counts less than 3.5 X 10(3) cells/microL, and seven patients had a nadir platelet count less than 100 X 10(3) cells/microL. Serial biopsies and blood samples were obtained in selected patients to evaluate the effect of MTX on tissue and lymphocyte phosphoribosylpyrophosphate (PRPP) and PRPP synthetase levels.
Effective control of chemotherapy-induced nausea and vomiting with oral prednisone and metoclopramide.
Authors: Senn H J , Glaus A , Bachmann-Mettler I
Published: February 2017

Repeated oral doses of metoclopramide (50 mg) and prednisone (25 mg) completely prevented nausea and vomiting (N + V) in approximately 50% and substantially reduced N + V in an additional 27%-36% of 56 chemotherapy courses in 30 consecutive cancer patients who were receiving primarily cisplatin. Toxicity from this antiemetic regimen was minor. Simple oral N + V-prevention with metoclopramide and prednisone is as effective but less cumbersome and considerably less expensive than either high doses of intravenous corticosteroids and/or intravenous metoclopramide.
Intensive chemotherapy, total body irradiation, and autologous marrow transplantation for chronic granulocytic leukemia-blast phase: report of four additional cases.
Authors: Phillips G L , Herzig G P
Published: February 2017

Four patients with Philadelphia chromosome (Ph1)-positive chronic granulocytic leukemia (CGL) in blast phase received cyclophosphamide, total body irradiation, and autologous marrow transplants using cryopreserved marrow from the stable phase. Two patients fully reestablished stable-phase leukemia that lasted for 26 and six months; the first patient developed transient Ph1-negative hematopoiesis after transplantation. Three patients eventually died of recurrent blast-phase leukemia. Previous studies using autologous marrow for CGL have reported an occasional long survivor, but incomplete engraftment and especially the rapid recurrence of blast-phase leukemia have been responsible for the overall poor results. The latter problem complicates even normal marrow transplantation, indicating the inadequacy of the current therapeutic regimens used for treating blast-phase leukemia and the possibility of improving results with more effective regimens and autologous marrow transplantation. Although it is unknown whether the reestablishment of Ph1-negative hematopoiesis after transplantation contributes to improved survival, this interesting phenomenon must be investigated further.
Chemotherapy-induced interstitial pneumonitis during treatment of small cell anaplastic lung cancer.
Authors: Zimmerman M S , Ruckdeschel J C , Hussain M
Published: February 2017

Twelve cases of interstitial pneumonitis were seen in 50 patients (24%) treated with cyclophosphamide, methotrexate, and etoposide (VP-16-213) for small cell anaplastic lung cancer. The clinical course and pathologic characteristics were consistent with drug-induced pneumonitis in all 12 cases. One additional patient had concurrent histologic evidence of interstitial pneumonitis, pneumocystis infection, and perivascular metastases. Patients presented with severe dyspnea, hypoxemia, cough, fever, and bilateral interstitial infiltrates on chest films. The onset was rapid and unpredictable, following as little as one month or as much as five months of therapy. Nine patients recovered but there were three deaths in the acute period directly attributable to the drug-induced pneumonitis. Although the use of twice weekly oral methotrexate may have been a causative factor, a previously unsuspected drug interaction with etoposide may be the etiologic factor resulting in this unusually high incidence of pulmonary toxicity. The difficulty in establishing a diagnosis of interstitial pneumonitis in this group of patients with chronic lung disease and lung cancer is well known. The extent of morbidity and mortality seen in this study and the commercial availability of etoposide make earlier clinical recognition of this complication imperative.
A comparison of fast homoarginine-sensitive alkaline phosphatase and carcinoembryonic antigen as markers in colon carcinoma.
Authors: Larson F C , Kahan L , Tormey D C , Davis T E
Published: February 2017

The diagnostic value of a recently described cancer marker, fast homoarginine-sensitive alkaline phosphatase ( FHAP ), was compared with the established marker, carcinoembryonic antigen (CEA), in the diagnosis of colon cancer. Comparisons were made with respect to sensitivity, specificity, predictive value of a positive result, and efficiency. An upper limit of normal of 2.1 units/L was assumed for FHAP , based on earlier studies. Two values for the upper limit of normal for CEA were tested: 2.5 ng/mL and 5.0 ng/mL. When 2.5 ng/mL was used as the upper limit of normal for CEA, FHAP was less sensitive, more specific, and had a higher predictive value. The diagnostic efficiency was not significantly different. When the upper limit of normal for CEA was set at 5.0 ng/mL, the two tests were roughly equal in sensitivity, specificity, predictive value, and diagnostic efficiency.
Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study.
Authors: Livingston R B , Mira J G , Chen T T , McGavran M , Costanzi J J , Samson M
Published: February 2017

The Southwest Oncology Group entered 453 patients with extensive small cell carcinoma into a combined modality treatment program, involving a randomized comparison of three different chemotherapy regimens for remission induction, and of maintenance chemotherapy alone versus maintenance treatment with cycles of reinduction added at six and 12 months. In addition, there was systematic comparison of diagnosis by institutional pathologist versus review panel pathologist. No difference was observed among the three different induction arms with respect to the incidence of response to treatment (61%), complete response (16%), or survival duration (median, 31 weeks). Neither overall response rate nor survival are superior to previous results. However, patients who achieved a complete response demonstrated significant survival benefit if they were in the group who received reinduction chemotherapy, as opposed to maintenance alone. This observation may apply most importantly to patients with small cell lung cancer of limited extent, for whom complete response is achieved in a majority. Agreement of institutional and review panel pathologists on the diagnosis of small cell lung cancer was observed in 94% of reviewed cases. A final observation is that the omission of chest irradiation results in a dramatic increase in the incidence of initial relapse at the primary tumor site. This suggests that future studies will need to use better therapy for local control in responding patients.
Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma.
Authors: King M E , Pfeifle C E , Howell S B
Published: February 2017

Previous pharmacokinetic modeling has suggested that cytosine arabinoside (ara-C) may be an ideal agent for peritoneal administration in the treatment of intraabdominal neoplasms. In vitro drug sensitivity testing with clonogenic assays demonstrated sensitivity to the high concentrations of ara-C potentially achievable by intraperitoneal (IP) administration in five of nine patients with ovarian carcinoma. The kinetics of IP ara-C were then studied in three patients, and a 2 to 3 log concentration gradient was observed between the peritoneal compartment and plasma. Subsequently, the clinical efficacy of IP ara-C given for a five-day course every four weeks was evaluated in 10 patients with ovarian carcinoma who had failed systemic chemotherapy. Chemical peritonitis did not occur and systemic toxicity was minimal. Two patients were rendered free of disease and are alive without disease 14+ and 15+ months since therapy was discontinued. These results demonstrate that there is a very large pharmacologic advantage to the IP route of administration for ara-C, that ara-C is active against advanced ovarian carcinoma, and that the IP route of administration permits the cytokinetically rational use of very long durations of exposure for this cell-cycle phase-specific agent.
Drug Concentration Errors Related to Sampling from Silastic Catheters
Authors: Quebbeman E. J. , Ausman R. K. , Hamid Ahmed A. R. , Caballero G. , Hoffman N. E.
Published: February 2017

To the Editor:

Constant infusion of some antitumor agents appears to improve their efficacy and/or diminish adverse effects associated with their administration. Silastic catheters placed for long-term central access facilitate this type of therapy. Also, they provide a means to obtain blood with minimal trauma for the patient. During treatment it is sometimes useful to withdraw samples for assay of drug blood levels. When doing so, we became concerned about unusually high 5-fluorouracil (5-FU) values in several patients, causing us to measure drug concentration in samples taken simultaneously from the catheter and a peripheral vein. Catheter samples showed seven to 80 times greater concentration of 5-FU. In one individual who had been off infusion for three days, a small 5-FU concentration persisted in the catheter sample whereas the peripheral vein value was zero as expected.

Subsequently, we performed an in vitro study. A Broviac catheter (volume, 0.6 mL) was perfused for five days at 2.0 mL per hour with a solution containing 500 mg 5-FU made up to 60 mL with 0.9% saline. The catheter then was flushed with 30-mL water to remove all fluid containing 5-FU. Ensuing sampling and flushing was done in accordance with Table 1. The last milliliter of flush solution was analyzed in each instance by high-pressure liquid chromatography technology.

Since all of the 5-FU infusion solution had been removed, the presence of drug in the water wash indicates that 5-FU was passing into the catheter lumen from the silastic wall.

We believe it is important to recognize that other drugs may act in the same way. The use of silastic catheters for both infusion and sampling may lead to an overestimation of drug concentration even though sufficient blood is withdrawn before taking the definitive sample.

Please see the PDF for Table.
The relevance of internal mammary lymphoscintigraphy in the management of breast carcinoma.
Authors: Ege G N , Elhakim T
Published: February 2017

The incidence, implications, and significance of an abnormal internal mammary lymphoscintigram (IML) in 981 breast carcinoma patients without histologic or clinical evidence of axillary metastases is reported. A 13%-16% incidence of parasternal abnormality in patients with early, operable disease correlates well with clinical data. The statistically significant increase, with P consistently less than or equal to 0.005, in incidence of local or distant relapse associated with an abnormal IML when compared to the normal IML emphasizes the value of the procedure as a marker. These results indicate that patients with negative axillae but an abnormal IML should be considered to have stage II disease and should be offered adjuvant therapy. The significance of the IML in determining the true extent of disease in patients with apparent local relapse as well as the prognostic implications of an abnormal IML in 311 patients seen initially with recurrent breast carcinoma is also reported.
Comparison of the antiemetic effect of high-dose intravenous metoclopramide and high-dose intravenous haloperidol in a randomized double-blind crossover study.
Authors: Grunberg S M , Gala K V , Lampenfeld M , Jamin D , Johnson K , Cariffe P , Strych D , Krailo M
Published: February 2017

Metoclopramide is an effective antiemetic for cisplatin-induced vomiting when given in parenteral high-dose regimens but not oral low-dose regimens. Metoclopramide was compared to haloperidol, also given in a high-dose parenteral regimen. Patients received two cycles of cisplatin at a dose greater than or equal to 70 mg/m2. Metoclopramide (2 mg/kg intravenous) was given every two hours for five doses beginning one half hour before cisplatin. Haloperidol (3 mg intravenous) was given on the same schedule. A randomized double-blind crossover design was used to control subjective bias and to compare the same patient's experiences. Twenty-eight patients completed both study arms. Excellent control of vomiting was achieved with both drugs. Metoclopramide resulted in 1.92 vomiting episodes (range, 0-5) with 36% having no vomiting. Haloperidol resulted in 3.04 vomiting episodes (range, 0-8) with 20% having no vomiting. Significantly fewer vomiting episodes were noted with metoclopramide rho = .006, paired sign test). However, responses to the two drugs were well correlated (Spearman's rho = .39, P = .03). Metoclopramide and haloperidol are both excellent antiemetics when given in sufficient dosage by an effective route. Metoclopramide does show a mild advantage. However, the positive correlation in response to these agents suggests a common mechanism of action. The ability to identify related antiemetics will be useful in the design of rational combination antiemetic therapy.
A phase I-II trial of cisplatin and dichloromethotrexate in squamous cell cancer of the head and neck.
Authors: Wheeler R H , Natale R B , Roshon S G , Baker S R
Published: February 2017

Dichloromethotrexate, a dihalogenated analog of methotrexate, is excreted and metabolized by the liver; therefore, blood levels are not dependent on renal function. The possibility that dichloromethotrexate could be given at its maximally tolerated dose in combination with high-dose cisplatin has been evaluated in 30 patients with advanced squamous cell cancer of the head and neck. Overall, this regimen was well tolerated, and 13 of 24 evaluable patients had an objective response to therapy (25% complete response and 29% partial response). The maximum dose of dichloromethotrexate that could be delivered was related to the serum albumin. Patients with an albumin less than 3.8 g/100 mL rarely tolerated doses of 500 mg/m2 or greater. Cisplatin plus dichloromethotrexate is an active drug combination in squamous cell cancer of the head and neck, and deserves further evaluation in randomized studies and in an adjuvant setting.
Isolated testicular relapse in acute lymphocytic leukemia of childhood: categories and influence on survival.
Authors: Bowman W P , Aur R J , Hustu H O , Rivera G
Published: February 2017

Isolated testicular relapse complicating first hematologic remission was identified in 31 of 521 boys with acute lymphocytic leukemia (ALL). Three categories of involvement were apparent and could be related to presenting clinical features, duration of initial complete remission, and length of hematologic remission. Among 12 patients with early testicular relapse, most had unfavorable prognostic features when ALL was first diagnosed. All but two of these children experienced marrow recurrence within seven months of testicular relapse. In contrast, the 12 patients who developed testicular disease late in their clinical course have responded much better to further therapy; ten remain in bone-marrow remission for a median of four years beyond testicular relapse. Similarly, five of the seven patients with subclinical testicular leukemia, found at elective biopsy, continue in marrow remission for prolonged periods. Early testicular recurrence is a sign of drug-resistant disease; late recurrence after elective cessation of therapy may represent residual, incompletely treated but still responsive leukemia.
Only By Products From Many Adjuvant Breast Cancer Studies
Authors: Sauter Christian
Published: February 2017

To the Editor:

The paper by Lippman et al prompts me to send you the following letter that might induce chairpersons of cooperative studies to reflect on the possibility that they may lose years of study time due to inadequate study designs.

The report of Lippman et al shows a typical adjuvant breast cancer study where, on the grounds of the study design, only by-products can be expected as results. Surgery-only control subjects were omitted from the study design based on the hypothetical but until today never-proven efficacy of doxorubicincyclophosphamide combination chemotherapy in the adjuvant situation. The main aim of any adjuvant study, if treatment is better than nothing, can not be answered by such a study design. Thus, secondary problems such as the tolerance of cytotoxic drugs after irradiation are studied. In another recently published study, by 1974 surgery-only control subjects were already omitted in an adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) trial. The three treatment arms (CMF, CMF plus tamoxifen, and CMF plus tamoxifen plus BCG) showed no difference in time to relapse. To extract at least some useful information the prognostic value of progesterone receptors were analyzed. However, the hundreds of CMF cycles were unnecessary for this information. The similarly designed 1976 Swiss study (chlorambucil, methotrexate, and fluorouracil [LMF] for six months v LMF for 24 months) will only demonstrate the known fact of the oncogenicity of chlorambucil. The lessons from such insufficient study designs unfortunately have not been learned in the eighties: The Ludwig Institute V trial on perioperative and adjuvant treatment lacks adequate surgery-only groups for an important prognostic subset (node-positive postmenopausal patients). For this subset the recent publication of the side effects will probably be the only useful information; however, this type of result never justifies the chemotherapy-induced suffering of these women. The new Swiss trial implemented in 1982 that compares CMF v LMF without surgery-only control subjects in one to three node-positive patients is an example of unnecessary chemotherapy (CMF in node-positive postmenopausal women.)

From all the studies without adequate control subjects, the best results we can expect are the type of results presented by Lippman et al. With respect to advances in therapeutic decision making, the years spent on these studies are lost.
A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer.
Authors: Muss H B , Kempf R A , Martino S , Rudnick S A , Greiner J , Cooper M R , Decker D , Grunberg S M , Jackson D V , Richards F
Published: February 2017

Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.
A comparison of computed tomography and radionuclide scanning for detection of brain metastases in small cell lung cancer.
Authors: Crane J M , Nelson M J , Ihde D C , Makuch R W , Glatstein E , Zabell A , Johnston-Early A , Bates H R , Saini N , Cohen M H
Published: February 2017

Neurologic history and examination, radionuclide brain scans (RN), and computed tomographic brain scans (CT) were performed at diagnosis and sequentially in 153 consecutive patients with small cell lung cancer (SCLC) to assess the sensitivity and accuracy of these screening methods and to determine whether the early detection of brain metastases influences survival. CT scans (sensitivity, 98%; positive predictive accuracy, 98%) were superior to RN scans (sensitivity, 71%; positive predictive accuracy, 86%) in patients with or without neurologic signs or symptoms. However, CT scans were positive in only 6% of asymptomatic patients at diagnosis and 13% of asymptomatic patients after systemic therapy. Brain metastases detected by CT scan were the sole site of extensive-stage disease in 6% of patients at diagnosis. Despite the enhanced ability of CT scans to detect asymptomatic lesions, survival after therapeutic cranial irradiation was similar for asymptomatic and symptomatic patients. The results suggest that CT brain scans should be used routinely in SCLC patients with neurologic signs or symptoms, at diagnosis (when treatment decisions are based on stage), and at six-month intervals in patients with prior brain metastases and in whom erratic follow-up is likely.
Co-trimoxazole prophylaxis during high-dose chemotherapy of small-cell lung cancer.
Authors: Figueredo A T , Hryniuk W M , Strautmanis I , Frank G , Rendell S
Published: February 2017

In 103 patients with small-cell lung cancer, we compared four courses of standard doses of Adriamycin (A) (Adria Laboratories, Columbus, Ohio), vincristine (V), and cyclophosphamide (C) with a regimen of increased doses of cyclophosphamide and to a lesser extent, Adriamycin. We found no significant difference in rate (22% v 21%) or median duration (seven v nine months) of complete remission. Patients not in complete remission after the four cycles of AVC received two courses of VP-16 (etoposide) and cisplatin: the complete remission rate increased to 49% and 48% respectively. Patients on the high-dose arm received co-trimoxazole prophylaxis; those on the standard arm did not. Patients on the high-dose arm had a higher incidence of neutropenia (nadir less than 500 cells/microL) but a lower incidence of infection for similar degrees of neutropenia. However, they also suffered more severe side effects of a different kind. Cotrimoxazole thus allowed for the administration of higher doses of chemotherapy to outpatients by protecting them from infection. However, the higher doses of cyclophosphamide and Adriamycin, did not improve treatment results, produced more severe side effects, and is not recommended.
Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer.
Authors: Evans W K , Osoba D , Feld R , Shepherd F A , Bazos M J , DeBoer G
Published: February 2017

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.
The human tumor clonogenic assay in human breast cancer.
Authors: Jones S E , Dean J C , Young L A , Salmon S E
Published: February 2017

The human tumor clonogenic assay (HTCA) was evaluated in 407 fresh samples of breast cancer from 288 patients. Seventy samples were inadequate for testing. Adequate in vitro growth for drug testing (greater than 30 colonies/plate) was obtained in 91 (27%) of the 337 viable samples, inadequate growth for drug evaluation (5 to 30 colonies/plate) in 17%, and no colony formation (less than 5 colonies/plate) in 56%. Operationally defining a greater than or equal to 50% inhibition of colony formation as in vitro drug sensitivity, the in vitro response rates to 12 anticancer drugs tested against ten to 36 different cancers (arranged in decreasing order according to the number of tests performed) were as follows: doxorubicin (14%), bisantrene (54%), vinblastine (33%), mitomycin (36%), interferon clone A (23%), 5-fluorouracil (20%), methotrexate (17%), leukocyte interferon (33%), mitoxantrone (42%), cyclophosphamide (25%), m-AMSA (16%), and melphalan (10%). Among 25 patients receiving single-agent therapy, there were ten (59%) of 17 with in vitro sensitivity who responded; resistance was correctly predicted in nine patients (100%), P = .01. Among 34 patients treated with combination chemotherapy, seven (50%) of 14 with in vitro sensitivity responded, and resistance was predicted in 13 (65%) of 20 patients. Difficulties in using the HTCA in breast cancer (including small specimen size, difficulties in disaggregation, and inadequacy of growth) will require additional research. Nonetheless, the assay appears to detect in vitro activity as well as resistance of a variety of anticancer agents and appears to predict clinical responsiveness to standard as well as some investigational single agents.
The rationale for planned reoperation after unplanned total excision of soft-tissue sarcomas.
Authors: Giuliano A E , Eilber F R
Published: February 2017

Multimodality management of soft-tissue sarcomas of the extremity is often based on the presence or absence of residual primary disease. Reoperation is warranted or radiotherapy doses altered if the physician is aware that the tumor was incompletely excised. Most patients with soft-tissue masses undergo an initial excision before definitive therapy. These initial unplanned total excisions are usually excisional biopsies for presumably benign disease. Ninety patients were reviewed to evaluate the adequacy of unplanned total excision. All patients underwent unplanned supposed total excisions. Most patients were then treated with preoperative intraarterial Adriamycin (Adria Laboratories, Columbus, Ohio) and radiation therapy, followed by wide reexcision of the prior operative field. Forty-six patients (51.1%) had no gross residual tumor in the reoperative specimen. In two patients, there was microscopic but not macroscopic disease. Forty-four patients (48.9%) had identifiable macroscopic residual disease in the reoperative specimen. When comparing these 44 patients with visible (macroscopic) residual tumor to the remaining 46, no differences were seen in age, sex, stage, histologic type, time from excision to reoperation, or size of initial lesion. This previously unrecognized high incidence of gross residual disease must be considered when planning definitive therapy. Unplanned total excisions are inadequate to remove local disease and, despite multimodality therapy, may result in local failure. Reoperation should be a planned part of definitive management for patients with soft-tissue sarcoma of the extremity whenever the initial surgical procedure was done without a histologic diagnosis or was not planned to be a wide excision. If reoperation cannot be performed, radiotherapy doses to treat gross residual disease should be used.
Psychological outcome of extremity sarcoma survivors undergoing amputation or limb salvage.
Authors: Weddington W W , Segraves K B , Simon M A
Published: February 2017

When compared to amputation, limb salvage procedures for extremity sarcomas have been advocated because of potential functional benefits and presumed psychological-outcome advantages. The purpose of this study was to compare psychological outcomes between survivors who underwent either amputation or limb salvage procedures for extremity sarcomas. Fifteen amputees and 20 patients with salvaged limbs (mean age, 37.9 years; range, 15 to 71 years) were evaluated 1 to 5 years after surgery for extremity sarcomas. Demographic and medical information was obtained and cognitive functioning, affect, mood, body image, physical functioning, global psychological adjustment to illness and surgery, and lifetime prevalence of psychiatric disorders before and after surgery were assessed. Two patients were excluded because of the presence of an incapacitating organic mental syndrome. The remaining patients, 14 amputees and 19 patients with salvaged limbs, had a variety of soft-tissue and bone sarcomas. No significant differences were found between the groups in age, sex, marital status, surgically involved extremity, chemotherapy status, and social class at the time of surgery and interviews. There were no significant differences between the groups in scores of cognitive capacity, symptoms, mood, body image changes, global physical functioning, global adjustment to illness and surgery, and lifetime prevalence of psychiatric disorders before or after surgery. Most patients revealed only mild psychological symptoms and 55% demonstrated good to excellent adjustment to their surgeries and diseases. There were no significant differences in measures of psychological outcome for patients with extremity sarcomas who underwent limb salvage procedures compared to those who underwent amputation. A psychological-outcome advantage of limb-salvage surgery compared to amputation has yet to be demonstrated.