Partial Regression Of Disease Research Articles

A combination of β-hydroxybutyrate and citrate ameliorates disease progression in a rat model of polycystic kidney disease.

Our research has shown that interventions producing a state of ketosis are highly effective in rat, mouse, and cat models of polycystic kidney disease (PKD), preventing and partially reversing cyst growth and disease progression. The ketone β-hydroxybutyrate (BHB) appears to underlie this effect. In addition, we have demonstrated that naturally formed microcrystals within kidney tubules trigger a renoprotective response that facilitates tubular obstruction clearance in healthy animals but, alternatively, leads to cyst formation in PKD. The administration of citrate prevents microcrystal formation and slows PKD progression. Juvenile Cy/+ rats, a nonorthologous PKD model, were supplemented from 3 to 8 wk of age with water containing titrated BHB, citrate, or in combination to find minimal effective and optimal dosages, respectively. Adult rats were given a reduced BHB/citrate combination or equimolar control K/NaCl salts from 8 to 12 wk of age. In addition, adult rats were placed in metabolic cages following BHB, citrate, and BHB/citrate administration to determine the impact on mineral, creatinine, and citrate excretion. BHB or citrate alone effectively ameliorates disease progression in juvenile rats, decreasing markers of cystic disease and, in combination, producing a synergistic effect. BHB/citrate leads to partial disease regression in adult rats with established cystic disease, inhibiting cyst formation and kidney injury. BHB/citrate confers benefits via multiple mechanisms, increases creatinine and citrate excretion, and normalizes mineral excretion. BHB and citrate are widely available and generally recognized as safe compounds and, in combination, exhibit high promise for supporting kidney health in polycystic kidney disease.NEW & NOTEWORTHY Combining β-hydroxybutyrate (BHB) and citrate effectively slows and prevents cyst formation and expansion in young Cy/+ rats using less BHB and citrate than when used alone, demonstrating synergy. In adult rats, the combination causes a partial reversal of existing disease, reducing cyst number and cystic area, preserving glomerular health, and decreasing markers of kidney injury. Our results suggest a safe and feasible strategy for supporting kidney health in polycystic kidney disease (PKD) using a combination of BHB and citrate.

Unsedated Office-Based Thulium Laser Therapy in Patients With Reinke's Edema

To report the outcome of unsedated office based Thulium laser therapy for Reinke's edema. A retrospective chart review of patients operated between March 2017 and November 2018 was conducted. Twelve patients were included, two of whom had two procedures performed. Demographic data included age, gender, smoking status, and grade of Reinke's edema. Outcome measures included Voice Handicap Index-10 (VHI), perceptual evaluation, extent of disease regression, acoustic analysis, and maximal phonation time. Twelve patients were enrolled in this study, one of whom was lost for follow-up. There were eight females and three males. The mean age was 51.27 ± 9.12 years. Endoscopic evaluation 6-12 weeks after surgery revealed complete and partial regression of disease in three and eight patients, respectively. There was a significant improvement in the mean score of VHI-10 (15.00 ± 9.45 vs 3.07 ± 3.81) and the mean score of GRABS parameters following surgery (P < 0.05). The mean habitual pitch increased from 125.11 ± 28.48 Hz to 155.86 ± 55.14 Hz (P=0.070). There was improvement in the mean jitter and shimmer but none reached a statistical significance. There was no significant change in the mean Maximum phonation time (MPT) scores before and after surgery. Unsedated office-based Thulium laser therapy can be considered as an alternative therapy to patients with Reinke's edema who are not willing to undergo conventional microlaryngeal surgery.

Prolonged Progression-Free Survival with Partial Disease Regression in Advanced Metastatic Medullary Thyroid Carcinoma Treated with Vandetanib

Objective: Medullary thyroid cancer (MTC), derived from thyroidal parafollicular C-cells, is a difficult treatment problem when presenting with advanced and meta-static disease. The recent addition...

Abstract B38: Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells

Abstract Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone-marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1 specific allorestricted T-cell receptor (TCR) wild-type and transgenic cytotoxic (CD8+) T cells against ES. Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide specific allorepertoire-derived (i.e., allorestricted) CD8+ T cells. Patient #1 received up to 4.8 x 105/kg body weight HLA-A*02:0 allorestricted donor-derived wild type CD8+ T cells. Patient #2 received up to 8.2 x 106/kg HLA-A*02:01 donor-derived and patient #3 up to 6 x 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319). Findings: HLA-A*02:01/CHM1319 specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft-versus-host disease (GVHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T-cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks. Interpretation: HLA-A*02:01/antigen specific allorestricted T cells proliferate in vivo without causing GVHD. CHM1319 TCR transgenic T cells home to affected BM and are associated with partial disease regression. Funding: Wilhelm Sander-Stiftung (2006.109.1), Else Kröner-Stiftung (GR &amp; SB; P31/08//A123/07), BMBF (GR, UT and SB, TranSarNet 01GM1104B; SB, PROVABES 01KT1311) and Cura Placida Children's Cancer Research Foundation. PHS is funded by the Excellenzinitiative at TUM/CCC Munich. Citation Format: Uwe Thiel, Sebastian J. Schober, Ingo Einspieler, Andreas Kirschner, David Schirmer, Katja Gall, Oxana Schmidt, Thomas G. P. Grunewald, Poul H. Sorensen, Guenther H. S. Richter, Irene Teichert von Luettichau, Dirk H. Busch, Stefan Burdach. Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B38.

Abstract 3757: Ewing Sarcoma regression by Allo-MHC/Chm1 specific T cells without GVHD

Abstract Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/ CHM1 specific allorestricted T cell receptor (TCR) wildtype and transgenic cytotoxic (CD8+) T cells against ES. Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide specific allorepertoire-derived (i.e. allorestricted) CD8+ T cells. Patient #1 received up to 4.8x105/kg body weight HLA-A*02:01- allorestricted donor derived wild type CD8+ T cells. Patient #2 received up to 8.2x106/kg HLA-A*02:01- donor derived and patient #3 up to 6x106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1319. Results: HLA-A*02:01/CHM1319 specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft versus host disease (GVHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks. Conclusions: CHM1319-TCR transgenic T cells home to affected BM and may cause partial disease regression. HLA-A*02:01/antigen specific allorestricted T cells proliferate in vivo without causing GVHD. Citation Format: Uwe Thiel, Sebastian Schober, ingo Einspieler, Andreas Kirschner, David Schirmer, Thomas Grünewald, Irene Teichert-von Lüttichau, Guenther Richter, Poul Sorensen, Stefan Burdach. Ewing Sarcoma regression by Allo-MHC/Chm1 specific T cells without GVHD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3757. doi:10.1158/1538-7445.AM2017-3757

Ewing sarcoma partial regression without GvHD by chondromodulin-I/HLA-A*02:01-specific allorestricted T cell receptor transgenic T cells

ABSTRACTBackground: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) wild-type and transgenic cytotoxic (CD8+) T cells against ES.Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide-specific allorepertoire-derived (i.e., allorestricted) CD8+ T cells. Patient #1 received up to 4.8 × 105/kg body weight HLA-A*02:01− allorestricted donor-derived wild-type CD8+ T cells. Patient #2 received up to 8.2 × 106/kg HLA-A*02:01− donor-derived and patient #3 up to 6 × 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319).Results: HLA-A*02:01/CHM1319-specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft versus host disease (GvHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks.Conclusions: CHM1319-TCR transgenic T cells home to affected BM and may cause partial disease regression. HLA-A*02:01/antigen-specific allorestricted T cells proliferate in vivo without causing GvHD.

Abstract A81: Adoptively transferred Chondromodulin 1/HLA-A:0201 allo-restricted T cell receptor transgenic CD8+ T cells are well tolerated and cause partial regression in a patient with disseminated Ewing Sarcoma

Abstract Background: Patients with Ewing sarcoma (ES) metastatic to bone and bone marrow (BM) do not survive irrespective of therapy. We assessed toxicity, viability, BM homing and anti-tumor activity of adoptively transferred HLA-A*0201/chondromodulin 1 (CHM1) allo-restricted T cell receptor (TCR) transgenic CD8+ T cells in an ES patient with refractory disease including marrow. Patient and Methods: An twelve years old HLA-A2+ boy was diagnosed with ES of the right femur. After treatment according to the Euro-Ewing 2008 protocol he suffered early relapse 11 months after diagnosis. For relapse treatment he received MetaEICESS 2007 including consolidation with haploidentical stem cell transplantation (allo-SCT) from his HLA-A2- mother. Before and shortly after transplant the patient relapsed twice. Thereafter he suffered from progressive disease under combined rescue radiochemotherapy. Within one week after the last progression, he received 1 x 106/kg (1st transfer, d0) and 8.2 x 106/kg CHM1319-T cell receptor (TCR) transgenic donor CD8+ T cells (2nd transfer, d32; in combination with ipilimumab and nivolumab), respectively. A patient derived ES cell line was isolated. Results: CHM1319-TCR transgenic donor T cells showed specific in vitro lysis of the patient's ES cell line. One week after 1st transfer, CHM1319-TCR transgenic T cells stained CHM1319 multimer positive in BM but negative in peripheral blood (PB). After 2nd transfer, BM of posterior iliac spines as well as PB stained CHM1319 multimer positive at a high rate and RT-PCR and flow-cytometric CD99+/CD45- ES phenotype as well as partial PET-signal reduction were noted. Five further metastatic bone/ marrow compartments showed significant PET signal regression. The patient never developed GvHD symptoms and died of disease 10 weeks after 1st transfer due to resistant lung metastasis. Conclusions: CHM1319-TCR transgenic T cells home to affected BM and cause partial disease regression. These cells may proliferate in vivo for at least four weeks without causing GvHD. Citation Format: Uwe Thiel, Andreas Kirschner, Ingo Einspieler, Stefan Burdach. Adoptively transferred Chondromodulin 1/HLA-A:0201 allo-restricted T cell receptor transgenic CD8+ T cells are well tolerated and cause partial regression in a patient with disseminated Ewing Sarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A81.

Intratumoral Therapy With Interferon-α in a Locoregional Advanced Malignant Blue Nevus

Malignant blue nevi are a rare variant of cutaneous melanoma often associated with metastatic disease and poor prognosis. Information on the treatment of this condition is limited. This case study reports the use of intralesional interferon -alpha2b (IFN-alpha2b) as a salvage option in a male patient with a congenital blue nevus on the right buttock. After initial diagnosis, the primary lesion (lesion 1) was partially resected and the patient received aggressive treatment with radiotherapy and concomitant polychemotherapy (cisplatin, vinblastine, and dacarbazine). However, the lesion progressed and the patient was treated second-line with carboplatin, paclitaxel, and sorafenib. Although this treatment stabilized the primary lesion, at cycle 6, the patient developed a measurable locoregional metastasis (lesion 2). At this stage, the patient was treated with intralesional IFN-alpha2b twice weekly at lesion 2, followed by weekly intralesional IFN-alpha2b therapy to both lesions, which resulted in partial disease regression. Biweekly maintenance therapy with IFN-alpha2b administered to both lesions maintained a partial response (ongoing at 23+ mo) and allowed complete occupational rehabilitation. Thus, intralesional therapy with IFN-alpha2b may be a viable treatment option in patients with locally advanced melanoma who have progressed on prior radiotherapy, polychemotherapy, and/or multikinase antiangiogenic-based therapy.

Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology.

Pediatric onset mastocytosis usually presents as urticaria pigmentosa; and less often as diffuse cutaneous mastocytosis. While the literature indicates that disease often resolves, there has been a move to more aggressive therapy for mastocytosis early in life. We addressed the long term prognosis of pediatric-onset disease by examining 17 children with mastocytosis which we had reported on in 1989 [1]. We successfully contacted 15 of these patients and data was collected regarding their clinical status. Original bone marrow specimens were re-stained, re-examined, and correlated with disease outcome using consensus criteria. Three of five patients with persistent disease underwent repeat bone marrow biopsies. There was complete regression of disease as defined by cutaneous findings and symptoms (clinical disease severity) in 10 of 15 patients (67%). Three patients had major (20%) and two had partial regression of disease (13%). Repeat marrow examinations on three patients with persistent disease documented systemic mastocytosis based on marrow findings in one patient who had partial regression of disease and was the only patient with initial morphologic evidence of systemic disease. Of the remaining two patients, one demonstrated partial regression and the other major regression of disease; and neither had evidence of systemic mastocytosis. This study demonstrates that initial bone marrow biopsies were prognostic in that those without evidence of systemic disease experienced disease regression; and that the long term prognosis for children managed symptomatically with mastocytosis is highly encouraging.

Safety and Efficacy of Radionuclide Therapy with High-Activity In-111 Pentetreotide in Patients with Progressive Neuroendocrine Tumors

The intent of this study was to evaluate the safety and efficacy of high-activity 111In-pentetreotide in patients with neuroendocrine tumors. Thirty-two patients with pentetreotide-avid neuroendocrine tumors received therapy from August 2005 to November 2006. Fourteen (14) patients received 1 treatment and 18 patients received 2 treatments. Patients were followed an average of 12.73 months (range 1.2-24.5). Seventeen (17) patients (53%) had grade I or II hematologic toxicities, and 1 patient had grade III thrombocytopenia. One patient had grade II liver toxicity, which appeared 4 weeks after therapy and resolved on week 5. No patient had renal toxicity. Of the patients who completed 2 treatment cycles, 2 of 18 patients had partial disease regression, and 16 of 18 patients with previously progressive disseminated neuroendocrine disease achieved stable disease by imaging criteria. A decrease in serum tumor markers was observed in 14 of 18 patients given 2 therapies. A clinical response was achieved in 84% of the patients. Upon interim analysis, median survival was approximately 13 months (range 1.2-24.5). These results show that high-activity 111In-pentetreotide therapy is effective in patients with progressive disseminated neuroendocrine tumors.

Definitive treatment of intermediate stage laryngeal squamous cell (SCC/L) cancer with chemotherapy (CT)

5533 Background: Surgery and/or radiotherapy (RT) are definitive local treatment modalities for intermediate stage SCC/L. Methods: We have evaluated paclitaxel (T) 175/mg/m2 day 1, ifosfamide (I) 1000mg/m2/days 1–3 (with mesna), and cisplatin (P) 60mg/m2 day 1 for previously untreated patients (pts) with SCC/L, stage T2 –4, N0 –1, M0. To be eligible, the primary tumor had to be considered resectable with conservation laryngeal surgery. After TIP x 3, pts achieving partial disease regression (PR) proceeded to surgery. Patients achieving a histologic complete response (CR) received an additional 3 CT cycles and no local treatment. A preliminary report was provided previously (FRK Proc ASCO #906, 2002). This is a report of more mature results with focus on CR patients treated with chemotherapy alone. Results: From 10/97 until 8/03, 29 patients (20 M, 9 F; median age 58 years, range 20–79) were entered. Tumor stage ranged from T2 N0 - T4 N1; median follow up is 36 months. Ten pts (34%) achieved CR and 17 (59%) PR after CT. CR patients were monitored monthly. Videostroboscopy will show tumor shrinkage, normalization of mucosa, and dramatic improvement in phonatory approximation in 5 of 5 pts with true vocal cord involvement. Two of 10 CR patients have developed local recurrence, with one living and disease-free after RT. Eight pts are alive and recurrence-free. Of the entire group of 29, 6 pts have developed recurrence (6 local/regional and 1 distant). Two patients have required total laryngectomy and 3 RT. Twenty-four of 29 pts are alive and disease-free. One patient died of a second primary cancer. Conclusions: Systemic chemotherapy for intermediate stage SCC/L provides durable disease remission in some pts. This favorable early experience suggests that SCC/L is potentially curable with systemic therapy. However, treatment of larynx cancer with chemotherapy as a single modality remains highly experimental. No significant financial relationships to disclose.

Definitive treatment of intermediate stage laryngeal squamous cell (SCC/L) cancer with chemotherapy (CT)

5533 Background: Surgery and/or radiotherapy (RT) are definitive local treatment modalities for intermediate stage SCC/L. Methods: We have evaluated paclitaxel (T) 175/mg/m2 day 1, ifosfamide (I) 1000mg/m2/days 1–3 (with mesna), and cisplatin (P) 60mg/m2 day 1 for previously untreated patients (pts) with SCC/L, stage T2 –4, N0 –1, M0. To be eligible, the primary tumor had to be considered resectable with conservation laryngeal surgery. After TIP x 3, pts achieving partial disease regression (PR) proceeded to surgery. Patients achieving a histologic complete response (CR) received an additional 3 CT cycles and no local treatment. A preliminary report was provided previously (FRK Proc ASCO #906, 2002). This is a report of more mature results with focus on CR patients treated with chemotherapy alone. Results: From 10/97 until 8/03, 29 patients (20 M, 9 F; median age 58 years, range 20–79) were entered. Tumor stage ranged from T2 N0 - T4 N1; median follow up is 36 months. Ten pts (34%) achieved CR and 17 (59%) PR after CT. CR patients were monitored monthly. Videostroboscopy will show tumor shrinkage, normalization of mucosa, and dramatic improvement in phonatory approximation in 5 of 5 pts with true vocal cord involvement. Two of 10 CR patients have developed local recurrence, with one living and disease-free after RT. Eight pts are alive and recurrence-free. Of the entire group of 29, 6 pts have developed recurrence (6 local/regional and 1 distant). Two patients have required total laryngectomy and 3 RT. Twenty-four of 29 pts are alive and disease-free. One patient died of a second primary cancer. Conclusions: Systemic chemotherapy for intermediate stage SCC/L provides durable disease remission in some pts. This favorable early experience suggests that SCC/L is potentially curable with systemic therapy. However, treatment of larynx cancer with chemotherapy as a single modality remains highly experimental. No significant financial relationships to disclose.

Immune gene therapy for kidney cancer: the search for a magic trigger.

It is estimated that approximately 30,000 new cases of renal cell carcinoma (RCC) will be diagnosed in 2002 [1]. Approximately 20–30% of patients with RCC present with metastatic disease and their overall median survival is 6–8 months [2]. One of the most intriguing features of RCC is the dramatically favorable course of the disease in a small subset of patients [3]. Oliver et al. observed 73 patients with metastatic renal cell carcinoma without treatment [4]. In this series, 4% had complete and spontaneous regression of disease and 3% had partial regression of disease.

Efficacy of the combination of nilutamide plus orchidectomy in patients with metastatic prostatic cancer. A meta-analysis of seven randomized double-blind trials (1056 patients).

To review the efficacy of the combination of the anti-androgen nilutamide (Anandron) plus orchidectomy in patients with stage D prostate cancer who had received no previous treatment. The results of seven randomized double-blind trials were analysed. In these studies patients were followed up until progression of disease or withdrawal for other reasons. Bone pain, urinary symptoms, performance status, levels of prostatic acid phosphatase (PAP) and alkaline phosphatase (AP) were evaluated before treatment and after 1, 3, 6, 12 and 18 months of treatment. Bone scans and X-rays were taken every 6 months. The best objective response, the time of progression and the time of death were recorded. The changes from baseline in symptoms and levels of tumour markers at month six and the percentages of objective regressions in the two treatment groups were compared using the Cochran-Mantel-Haenszel test stratified by study. Peto's method was used for the analysis of time to progression and of survival. Of the 1191 patients enrolled in all the original trials, 1056 were eligible. In the group of patients treated with nilutamide 50% had complete or partial regression of disease compared with 33% of those who were given a placebo (P < 0.001); bone pain and levels of PAP and AP were improved or returned to normal significantly more frequently (P < 0.01); the odds of disease progression were significantly reduced (odds ratio 0.84, P = 0.05); the odds of death from cancer and from other causes were reduced but the difference was not statistically significant. The combination of nilutamide and orchidectomy has a beneficial effect on pain of metastatic origin, levels of tumour markers, the objective response of disease and the time to disease progression. This treatment combination might also improve survival.

Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study.

Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

Failure of bleomycin to improve the therapeutic effects of a combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) in advanced sarcomas.

Fifty-eight adults with unresectable metastatic sarcomas received monthly courses of bleomycin, cylcophosphamide, doxorubicin, and cisplatin (BCAP) in combination. Following four courses of BCAP, alternating monthly courses of vincristine, cyclophosphamide, dactinomycin and vincristine, doxorubicin, and dacarbazine were begun. Treatment was continued until disease progression or the achievement of disease resectability, with elimination of doxorubicin after a total dose of 520 mg/m2 had been received. Ten patients electively stopped treatment prematurely. One other patient was removed from treatment because of significant pulmonary toxicity. Of the 58 patients 20 (34%) achieved partial regression of disease including 10 of 18 with leiomyosarcoma, 2 of 8 with malignant fibrous histiocytomas, 3 of 8 with osteosarcoma, 3 of 7 with fibrosarcoma, 1 of 2 with epithelioid sarcoma, and 1 of 1 with mesenchymal chondrosarcoma. Median time to disease progression was 174 days and median survival was 341 days. The percentage of patients achieving disease regression on this study was nearly the same as the percentage achieving disease regression on study of CAP in advanced sarcomas.

Phase II trial of piperazinedione (NCS 135758) in the treatment of advanced or recurrent squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Thirty-eight patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to management with surgery and/or radiotherapy were given piperazinedione 9 mg/m2 intravenously every 3 weeks. Five (13%) experienced either complete or partial regression of disease, while 13 (34%) demonstrated stable disease. Responses were relatively short (median 3 months) with responders surviving significantly longer than nonresponders (median 20.3 months vs. 3.0 months, p = 0.01). Adverse effects consisted primarily of myelosuppression (61%) and nausea and vomiting (47%) and generally were mild to moderate and tolerable. The drug has minimal activity and tolerable adverse effects and could be considered for trials of combination chemotherapy in this disease.

Antioestrogens in treatment of breast cancer: value of nafoxidine in 52 advanced cases.

The synthetic non-steroidal antioestrogen nafoxidine (U-11, 100A) was given by mouth to 52 women with locally advanced or metastatic breast cancer, in 85% of whom the disease had become resistant to, or relapsed after, previous endocrine treatment. The objective response rate (complete or partial regression of disease) among 48 cases treated for at least four weeks was 37%. Tumours in soft tissue seemed to respond better than skeletal metastases. The patients in all but one of the 52 cases were postmenopausal. Those who had had an objective response to previous hormone treatment had a greater chance of deriving benefit from nafoxidine than those who had been resistant to hormone treatment.Side effects of nafoxidine were dryness of skin, increased loss of scalp hair, and heightened sensitivity to sunlight. None were serious, and they could be lessened by protection from solar radiation or a decrease in dosage. No obvious depression of thyroid or adrenal function or obvious water retention or masculinization was seen. Cataract was a possible complication.This clinical trial was preceded by laboratory studies in which a transplantable oestrogen-dependent tumour in the Syrian hamster was notably inhibited by the administration of nafoxidine. This experimental model may prove useful in screening potentially useful antioestrogenic agents against breast cancer before a human trial.

Results in fifty cases of advanced squamous cell carcinoma of the head and neck treated by intravenous chemotherapy.

The results of intravenous chemotherapy for advanced squamous cell carcinoma of the head and neck in 50 patients are presented. Forty patients were treated with methotrexate alone-3 patients showed partial regression of disease and a further 7 were controlled for periods of up to 4 months. Of those patients who failed to respond, or who relapsed on methotrexate, 16 were treated with combination chemotherapy. One patient showed complete regression of disease, 2 partial regression and in 2 others control was achieved for up to 4 months. A further 10 patients were treated with combination chemotherapy only, with no previous methotrexate. In this group no objective regressions were noted and only one patient was controlled for a period of 14 months. It is suggested that intravenous chemotherapy in advanced squamous cell carcinoma of the head and neck is of doubtful value.